Lentivirus from the group of immunodeficiency viruses of drill monkeys (Mandrillus leucophaeus) and their use

Abstract

The present invention relates to an immunodeficiency virus of drill monkeys, its RNA, the corresponding cDNA, proteins derived therefrom and fragments of the nucleic acids or proteins. The invention likewise relates to the diagnostic use of the nucleic acids and proteins mentioned and their fragments and to a diagnostic.

Description

The present invention relates to the immunodeficiency virus SIM27 of drill monkeys, whose RNA or a part thereof is complementary to the sequence shown below, and variants of this virus. Moreover, the viral RNA, the corresponding CDNA, proteins derived therefrom and fragments of the nucleic acids or proteins are a subject of the present invention. The invention likewise relates to the diagnostic use of the mentioned nucleic acids and proteins and their fragments, and a diagnostic comprising these nucleic acids and/or proteins and/or fragments thereof.

Primates have been developing for approximately 30 million years, which has lead to a high degree of variability of the individual primate species. The New World monkeys (Platyrrhini) are differentiated from the Old World monkeys (Catarrhini), which for their part are divided into the hominoids (Hominoidae) and the cercopithecoids (Cercopithecoidea). Together with the primates, various infective agents have also developed, which have adapted to the individual primate species or, for example, to a whole family. Examples of virus are the simian pathogenic and the human pathogenic herpesviruses, which although they can still infect individuals of another primate species, are naturally not transmitted from one primate species to the other. Other viruses still infect all primates, such as the rabies virus, the yellow fever virus and the filovirus.

Lentiviruses are subdivided into the genera of the spume viruses, the T-leukemia/lymphoma viruses and the immunodeficiency viruses. A general survey of the leukemia and immunodeficiency viruses of the monkeys and their pathogenicity is found in the article of Hayami (Hayami M et al., Curr. Top. Microbiol. Immunol. 1994; 188: 1-20). Spume viruses appear to occur only in monkeys. Since until now a pathogenicity of the spume viruses has not been detected, this virus is being less intensively investigated than HIV/SIV and HTLV/STLV.

HTLVs, the human T-leukemia viruses type I and type II, are structurally very similar to STLVs, the simian (monkey) T-lymphoma viruses (Franchini et al., AIDS Res Human Retrovirus 1994; 10: 1047-1060). Thus the difference in the virus species, STLV I and II, and the viruses between man (HTLV) and monkeys (STLV) is a sign of a long individual evolution in the individual primates, if a cross-transmission between the various primate species can be excluded (Franchini et al., AIDS Res Human Retrovirus 1994; 10: 1047-1060). STLV-infected monkeys occur over the entire world (Hayami M et al., Curr. Top. Microbiol. Immunol. 1994; 188: 1-20), whereas SIV-infected monkeys are only to be found naturally in Africa, which is an indication of the fact that SIV very probably developed later than STLV.

Molecular biology results show clearly that HIV-1 is very closely related to the immunodeficiency viruses of the chimpanzee. The latter viruses are subsequently designated as SIV-1, whereas the virus of the mangabeys, SIVsm, is designated as SIV-2. SIV-1 and HIV-1 derive with high probability from a precursor virus, just as SIV-2 and HIV-2 probably have a common precursor. Up to 25% of troops monkeys can naturally be infected with SIV-2 without signs of the virus pathogenesis being detectable in the infected animals (Chen Z et al., J Virol. 1996; 70: 3617-3627). In the case of SIV-2, infections in man were detected which do not differ in their pathogenesis from an HIV-2 infection. SIV-2 is closely related to HIV2 and particularly epidemically widespread in West Africa south of the Sahara, in the same region in which the mangabeys live (Gao FL et al., Nature 1992; 358: 495-499). The results of the investigations on SIV show that in addition to the SIV-2 (SIVsm) of mangabeys the immunodeficiency viruses of the African green meerkat represent a further type, perhaps SIV-3, and in addition meanwhile some further simian SIVs have been isolated which cannot be assigned to the groups of viruses mentioned and which probably represent the SIV type 4. This SIV-4 type is formed by the viruses of the Sykes monkeys (Cercopithecus mitis), the Hoest monkeys (Cercopithecus 1′hoesti) (Hirsch VM et al., J. Virol. 1999; 73: 1036-1045), the red cap mangabeys (Cercopithecus torquatus torquatus) (Georges-Courbot MC et al., J. Virol. 1998; 72: 600-608), the mandrill monkeys SIVmnd (Mandrillus sphinx) (Tsujimoto H et al., Nature 1989; 341: 539-541), and the drill monkeys (Mandrillus leucophaeus) (Clewley JP et al., J. Virol. 1998; 72: 10305-10309). All previously isolated SIV-4s can be cultured in human peripheral blood lymphocytes and some in the human permanent cell line Molt4 clone 8 (Hirsch VM et al., J. Virol. 1999; 73: 1036-1045), which indicates that the infection of man with these viruses should also be possible. The SIV-4 type is so different from the SIV-2 type that an SIVmac(SIV2)-specific p25 antigen test cannot detect SIVhoest (SIV4) produced in the supernatant of infected cells (Hirsch VM et al., J. Virol. 1999; 73: 1036-1045), as the Gag region is too divergent for recognition by monoclonal antibodies. The phylogenetic comparison of the nucleic acid sequences of the simian viruses also shows that the SIV-4 described here differs from SIV-2 and SIV-3 (Korber et al. Human Retroviruses and AIDS 1997. A compilation and analysis of nucleic acid and amino acid sequences. Los Alamos National Laboratory, New Mexico, 1998).

As described above, a virus similar to SIVcpz is possibly the precursor virus of viruses causing human HIV-1 infections, which the high similarity of viruses of the group HIV1-M, −N and −O to SIV-1 indicates.

To date, there are no reports that humans have been infected with SIV-4. A nosocomial infection with SIV-3 or SIV-2 occurred due to contamination of the eczematous skin of a laboratory assistant (Khabbaz RF et al., N. Engl. J. Med. 1994; 330: 172-177). The SIV replicated for a certain time which was sufficient for the induction of a strong antibody response, but was not sufficient to establish a permanent infection (Khabbaz RF et al., N. Engl. J. Med. 1994; 330: 172-177). About 3.5 years after seroconversion, the laboratory assistant appeared to be free of the infection (Khabbaz RF et al., N. Engl. J. Med. 1994; 330: 172-177). Whether this path of virus elimination is the rule or whether persistent infections with corresponding pathogenesis can also result from the infective event is unknown.

Since until now no epidemiological studies on target groups in central Africa have been carried out which can show whether variant viruses such as SIV-4 also circulate in the human population, infection of man cannot be confirmed, but can also not be excluded.

As was seen in the example of the HIV-1 subtype O, antibody detection tests on the basis of HIV-1 subtype M were not sufficiently reactive in order to be able to detect all subtype O-infected patients (Simon F et al. AIDS 1994; 8: 1628-1629). The diagnosis of an infection with an aberrant human pathogenic SIV subtype could probably also not be made, as it must be assumed that the ELISA exploratory tests based on HIV-1 and/or HIV-2 antigens are negative or would only be slightly reactive, and the attempt at confirmation by means of the immunoblot produced a negative or probably questionable result. The diagnosis could probably also not be made by means of the nucleic acid tests, since with the presently available tests, for example, neither the nucleic acid of the viruses of group O nor that of HIV-2 can be reliably amplified (Gürtler L et al., 12th World AIDS Conference Geneva Basic Science 1: 121-124).

The drill monkeys described here ( Mandrillus leucophaeus ) are animals which originate from the western region of Cameroon bordering Nigeria and live wild there in the bushland. Drill monkeys have become widespread in the central West-African region. The animals are hunted and eaten, which is why the stock in recent years has continuously decreased. Young animals are in some cases picked up and kept in the vicinity of the houses as pets. The monkey 27 described here (3 years old) was captured from a free hunting reserve and then domesticated over the course of a year and has had no contact with other monkeys of the same or of a similar species.

As described in Example 2, the virus originating from monkey 27 was replicated in human PBLs. Genomic DNA and thus also integrated proviral DNA of the SIV was isolated from the infected cells. The deciphering of the sequence of the total genome of the SIV is described in Example 3. The PCR (polymerase chain reaction) method was employed for the multiplication of the viral DNA. The components needed for carrying out the process can be acquired commercially.

Using this process, it is possible to amplify DNA sequences if DNA regions of the sequence to be amplified are known, or known sections are sufficiently similar. Short complementary DNA fragments (oligonucleotides=primers) which add to a short region of the nucleic acid sequence to be amplified must then be synthesized. For carrying out the test, nucleic acids are combined with the primers in a reaction mixture which additionally contains a polymerase and nucleotide triphosphates. The polymerization (DNA synthesis) is carried out for a specific time, then the nucleic acid strands are separated by warming. After cooling, the polymerization starts again.

The amplified genome sections were sequenced by the Sanger method. As described in Example 4, the genome of SIM27 was subjected to phylogenetic comparisons which showed that it is a strongly divergent novel simian immunodeficiency virus.

The present invention therefore relates to:

1.) Immunodeficiency viruses which branch off as a side branch from the SIM27 side branch after the branching of SIM27 in a phylogenetic investigation of their total genome on the nucleic acid plane, as is described in Example 4 (see FIG. 1 )

2.) GAG proteins and fragments thereof which branch off as a side branch from the SIM27 side branch after the branching of SIM27 in a phylogenetic investigation of their total sequence on the amino acid plane, as is described in Example 4 (see FIG. 2 ).

3.) Pol proteins and fragments thereof which branch off as a side branch from the SIM27 side branch after the branching of SIM27 in a phylogenetic investigation of their total sequence on the amino acid plane, as is described in Example 4 (see FIG. 4 ), or a POL protein fragment or subfragments thereof which branch off as a side branch from the SIM27 side branch after the branching of SIM27 in the region of the sequence including this amino acid sequence, published by Clewley (Clewley JP et al., J. Virol. 1998; 72: 10305-10309), as has been investigated as described in Example 4 (see FIG. 6 ).

4.) ENV proteins and fragments thereof which branch off as a side branch from the SIM27 side branch after the branching of SIM27 in a phylogenetic investigation of their total sequence on the amino acid plane, as is described in Example 4 (see FIG. 7 ).

Of particular interest is furthermore the consideration of the strongly immunogenic cysteine loop region in the Erxv gene, which is therefore of particular diagnostic importance. The cysteine-loop regions of various immunodeficiency viruses are shown in Table 1 (SEQ ID NOS: 26-57, respectively).

TABLE 1
S1M27.ENV	RLTALEEYVADQSRLAVWG	CSFSQVC	HTNVKW
SIV-Mandrill, MNDGB1	RLTSLENYIKDQALLSQWG	CSWAQVC	HTSVEW
HIV1-N,	YBF30	KVLAIERYLRDQQILSLWG	CSGKTIC	YTTVPW
HIV1-C,	96bw05.02	RILAVERYLKDQQLLGIWG	CSGKLIC	TTAVPW
HIV1-O,	ANT70C	RLLALETLLQNQQLLSLWG	CKGKLVC	YTSVKW
SIV-CPZ,	CPZGAB	RLLAVERYLQDQQILGLWG	CSGKAVC	YTTVPW
HIV1-O,	MVP5180	RLQALETLIQNQQRLNLWG	CKGKLIC	YTSVKW
SIV-1hoesti	RLTALEEYVKHQALLASWG	CQWKQVC	HTNVEW
SIV-SYKES	RLTALETYLRDQAILSNWG	CAFKQIC	HTAVTW
SIV-CPZ, CPZANT	RMLAVEKYLRDQQLLSLWG	CADKVTC	HTTVPW
SIV-CPZ-US	RVLAVERYLKDQQILGLWG	CSGKTIC	YTTVPW
HIV1-F,	93br020.1	RVLAVERYLKDQQLLGLWG	CSGKLIC	TTNVPW
HIV1-A,	92ug037	RVLAVERYLRDQQLLGIWG	CSGKLIC	PTNVPW
HIV1-H,	90cr056	RVLAVERYLRDQQLLGIWG	CSGKLIC	TTNVDW
HIV1-D,	NDK	RVLAVERYLRDQQLLGIWG	CSGRHIC	TTNVPW
HIV2-B,	UC1	RVTAIEKYLKDQALLNSWG	CAFRQVC	HTTVPW
SIV-D,	MNE	RVTAIEKYLKDQAQLNAWG	CAFRQVC	HTTVPW
SIV-D,	MM239	RVTAIEKYLKDQAQLNAWG	CAFRQVC	HTTVPW
SIV,	SME543	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
SIV-D,	SMM-PBJ-6P9	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
SIV-D,	STM	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
HIV2-A,	CAM2	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
HIV2-A,	GH1	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
HIV2-B,	EHO	RVTAIEKYLKDQAQLNSWG	CAFRQVC	HTTVPW
SIV-SMM,	PGM	RVTAIEKYRKDQAQLNSWG	CAFRQVC	HTTVPW
SIV-VERVET,	AGM155	RVTALEKYLADQARLNAWG	CAWKQVC	HTTVPW
SIV-VERVET,	AGM3	RVTALEKYLEDQARLNAWG	CAWKQVC	HTTVPW
SIV-SABAEUS,	AGMSAB1	RVTALEKYLEDQARLNIWG	CAFRQVC	HTTVLW
SIV-VERVET,	AGMTY6	RVTALEKYLEDQARLNSWG	CAWKQVC	HTTVEW
SIV-GRIVET,	AGM677A	RVTALEKYLEDQARLNSWG	CAWKQVC	HTTVPW
SIV-VERVET,	REV	RVTALEKYLEDQARLNVWG	CAWKQVC	HTTVPW
SIV-TANTALUS,	TAN1	RVTALEKYLEDQTRLNLWG	CAFKQVC	HTTVPW

As can be clearly seen, either lysine or arginine occurs in position 3 of the cysteine loop (C12345C) in nearly all representatives of immunodeficiency viruses. The only exception up to now was found in the immunodeficiency virus MNDGB1, which was likewise isolated from a drill monkey (Mandrillus spinx). With great probability it is to be assumed from this that antibodies formed against this modified epitope cannot be recognized or can be recognized with clearly decreased efficiency from diagnostic tests known up to now which are based on the customary arginine- or lysine-containing antigens.

This invention therefore likewise relates to antigens in which arginine and/or lysine within the cysteine loop region in position 3 has been replaced by any desired amino acid, particularly preferably a polar amino acid such as serine or an amino acid having an aliphatic side chain such as alanine.

The present invention is moreover described in the examples and in the patent claims, where the examples serve for summarization and no restriction of the present invention must be derived therefrom.

EXAMPLE 1

Identification of the SIM27 infection in drill monkeys

In the course of a study, EDTA blood was taken from drill monkeys in the villages of rural Cameroon, in which they were kept, and this was analyzed in various HIV tests. On testing the serum of the monkey SIM27 for antibodies, a competitive ELISA for HIV-1 was negative and an ELISA from Dade Behring (Enzygnost HIV-1/2 plus) recognizing HIV-1, −2 and −O was likewise negative, the extinction lying near the threshold value. In the analysis of the HIV-1 Western blot (virus MVP899-87) which was carried out at the same time, no virus-specific bands were to be seen, in the HIV-2 blot (virus MVP11971-87), the band gp36 was to be seen strongly, and the bands p55 and p68 were to be seen, and in the HIV-1 group O blot (virus MVP5180-91), the bands p24 and p55 were to be seen. Gp36 is the transmembrane protein of HIV-2, the bands p55 and p68 correspond to the reverse transcriptase (p55) plus the RNaseH (p68) of HIV-2, and p24 is the inner core protein of HIV-1 group O viruses and p55 the precursor protein of gag and thus also p24. 20 ml of plasma from the animals were employed in order to develop the Western blot. According to the analysis of the nucleic acid sequence, the virus MVP11971-87 is a representative of the group HIV-2A, the virus MVP899 a representative of HIV-1B.

The SIV infection of the monkeys with the drill virus is thus distinguished:

by negativity in normal screening ELISAs for HIV antibodies,

by serological cross reaction in the env and pol region with the HIV-2 transmembrane glycoprotein and the reverse transcriptase in the Western blot,

by serological cross reaction in the gag region with the inner core protein of HIV-1 group O and absent cross reaction with the core proteins of group M (HIV-1B) in the Western blot.

EXAMPLE 2

Isolation of the SIM27 Virus

The lymphocyte fraction was isolated by Ficoll gradient centrifugation from 5 ml each of EDTA blood of the monkeys. The lymphocytes were stimulated with PHA (phytohemaglutinih, 5 mg/ml) and PMA (myristylphorbol ester, 10 ng/ml), after 3 days both additives were washed out and the culture was continued in the presence of RPMI-1640, as usual, with interleukin-2 addition. The PMA stimulation was described by Kubo et al. (Kubo M et al., J. Virol 1997; 71: 7560-7566).

The culture conditions were similar to those which have been described by Tamalet et al. (Tamalet, C. et al., AIDS 1994; 1083-1088). After one week in culture, human PHA-stimulated and nonstimulated blood lymphocytes (PBLs) were added to the monkey lymphocytes and the addition was repeated once weekly until it was possible after about 3 weeks to detect beginning SIV production by means of a commercially obtainable p24 antigen test (Abbott, Wiesbaden).

The virus was then subcultured on human lymphocytes from the supernatant of the cells. All attempts to transfer the SIM27 to permanent culture cells such as HUT-78 or Jurkat have failed up to now. By means of monthly subculturing, it was possible to keep SIM27 on PBL in culture for 9 months from then on.

EXAMPLE 3

DNA Isolation, Amplification and Structural Characterization of Genome Sections of the HIV Isolate SIM27

Genomic DNA from SIM27-infected blood lymphocytes was isolated by standard methods (Current Protocols in Molecular Biology, Wiley Interscience, 1994).

The total genome was amplified exclusively by means of PCR (polymerase chain reaction). All PCRs were begun by means of “Hot Start”: after addition of all components of the PCR, except the polymerase, this was added only after heating the sample to 94° C., which strongly reduces the extension of nonspecifically binding primers.

A general survey of the individual stages of the deciphering of the genome is shown in FIG. 8 .

For the characterization of genome regions of the isolate SIM27, PCR experiments were carried out with primer pairs from the region of the integrase in the pol gene. The PCR (Saiki et al., Science 239: 487-491, 1988) was modified as follows:

For the first amplification of HIV-specific DNA regions, 5 μl (200 μg/ml) of genomic DNA from SIM27-infected blood lymphocytes were pipetted into a 50 μl reaction mixture (0.25 mM dNTP, 1 μM each primer, 10 mM tris HCl, pH 8.3, 50 mM KCl, 1.5 mM MgCl2, 0.001% gelatin, 2.5 units platinum-Taq DNA polymerase (Gibco)) and amplified according to the following temperature program:

1) initial denaturation: 3 min. 95° C.,

2) amplification: 30 sec. 94° C., 30 sec. 49° C., 30 sec. 68° C. (30 cycles).

The primers used for the PCR had the following sequence:

(Seq. ID No. 1 and 2)

5′3′

5 pol2380agm GCC ATG TGT CCA AAA TGT CA

3pol2930agm CTT CTC TGT AGT AGA CTC TA

5 μl of the amplificate were employed as a template for a second nested PCR with the following primers and the same temperature profile:

(Seq. ID No. 3 and 4)

5pol2460agm TAG TAG CAG TCC MYR KWG

(M=A/C,Y=C/T,R=A/G,K=G/T,W=A/T)

3pol2760agm TCT CTA ATT TGT CCT ATG AT

The amplificate thus obtained was sequenced directly without cloning.

The sequence found is shown in Table 2.

TABLE 2
(SEQ ID NO: 17):
1   AGTAGCAGTC CATGTAGCCA GTGGATACCT AGAGGCAGAA GTAATACCAG
51  CAGAGACAGG AAAAGAGACA GCACATTTCC TGTTAAAGTT AGCAGGCAGG
101 TGGCCTGTAA AACATTTACA CACTGACAAT GGCCCCAACT TTGTCAGTGA
151 AAAGGTAGCC ACAGTCTGTT GGTGGGCTCA AATAGAGCAC ACCACAGGTG
201 TACCCTATAA CCCCCAGAGT CAGGGAGTAG TGGAAGCAAA GAATCATCAT
251 CTTAAGACAA TCATAGGACA AATTAGAGA

Based on the publication of Clewley (Clewley JP et al., J. Virol 1998; 72: 10305-10309), a further amplificate was obtained in the 5′ region of the pol gene. The primers DR1, DR2 and, for the nested PCR, DR4 and DR5 described by Clewley were used, as well as the temperature cycles described in this publication. The polymerases used were DNA-Taq polymerase (Perkin Elmer) and the buffers described above.

The sequence according to Table 3 was obtained here:

TABLE 3
(SEQ ID NO: 18):
1   GGGATTCCGC ANCCGGCAGG TCTAAAACAA TGTGAACAGA TCACAGTATT
51  GGATATAGGA GATGCCTATT TTTCATGCCC ATTGGATGAG GACTTTAGAA
101 AGTATACTGC ATTCACCATT CCATCGGTGA ATAATCAGGG GCCCAGGAAT
151 CAGATACCAG TATAATGTCC TCCCNCAGGG NTGGAAGGGG TCCCC

In a next amplification, the region of SIM27 lying between the amplificates already obtained was amplified. The primers mentioned below were used here.

For the first PCR:

(Seq. ID No. 5 and 6)

1216 ATG CCC ATT GGA TGA GGA C

1197 GAC TGT GGC TAC CTT TTC ACT

For the nested PCR:

(Seq. ID No. 7 and 8)

1218 CAT CGG TGA ATA ATC AGG

1226 GGT ATT ACT TCT GCC TCT A

The platinum-Taq DNA polymerase (Gibco) was used according to the following temperature program:

1) initial denaturation: 2 min. 95° C.,

2) amplification: 30 sec. 95° C., 30 sec. 55° C., 150 sec. 68° C. (30 cycles).

The sequence according to Table 4 was obtained here.

TABLE 4
(SEQ ID NO: 19):
1   CATCGGTGAA TAATCAGGGC CCAGGAATCA GATACCAGTA TAATGTCCTC
51  CCACAGGGAT GGAAAGGCTC TCCAGCAATT TTTCAGGCAA CAGCTGATAA
101 AATCTTGAAA ACATTCAAAG AAGAATACCA GAGGTATTAA TTTATCAGTA
151 TATGGATGAT CTGTTCGTGG GAAGTGACTT AAATGCCACT GAACATAACA
201 AAATGATAAA CAAGTTGAGA GAGCATCTGA GATTCTGGGG GCTCGAGACC
251 CCAGATAAGA AGTTTCAAAA GGAACCTCCT TTTGAATGGA TGGGATATGT
301 GCTACACCCA AAGAAATGGA CAGTGCAGAA AATACAACTA CCAGAAAAAG
351 AGCAATGGAC AGTGAATGAT ATTCAGAAAT TGGTAGGAAA ACTTAATTGG
401 GCAAGTCAGA TATATTCCGG AATTAAAACA AAAGAGCTCT GTAAATTGAT
451 CAGAGGAGCA AAACCTCTAG ATGAAATAGT AGAATGGACA AGAGAAGCAG
501 AATTAGAGTA TGAAGAGAAT AAGATAATAG TGCAGGAGGA GGTGCATGGA
551 GTGTACTATC AGCCAGAAAA ACCACTGATG GCAAAAGTAC AAAAGTTGAC

The region of the total sequence of the 5′-LTR region of the genome up to the pol gene was amplified with the following primer pairs:

1. PCR:

(Seq. ID No. 9 and 10)

1248 CTC AAT AAA GCT TGC CTT GA

1217 GTC CTC ATC CAA TGG GCA T

2. Nested PCR:

10 (Seq. ID No. 11 and 12)

1249 TRD CTA GAG ATC CCT CAG A (R=A/, D=G/A/T)

1219 CCA ATA CTG TGA TCT GTT CAC

platinum-Taq DNA polymerase (Gibco) was in each used according to the following temperature program:

1) initial denaturation: 2 min. 95° C.,

2) amplification: 30 sec. 95° C., 30 sec. 50° C., 180 sec. 68° C. (30 cycles). 1×enhancer (Gibco) was used in addition to the buffers indicated above.

The sequence according to Table 5 was obtained here:

TABLE 5
(SEQ ID NO: 20):
1   TRDCTAGAGA TCCCTCAGAT TTGTGCCAGA CTTCTGATAT CTAGTGAGAG
51  TAGAGAAAAA TCTCCAGCAG TGGCGCCCGA ACAGGGACTT GACGAAGAGC
101 CAAGTCATTC CCACCTGTGA GGGACAGCGG CGGCAGCCRG CCGGACCGAC
151 CCACCCGGTG AAGTGAGTTA ACCAAGGAGC CCCGACGCGC AGGACACAAG
201 GTAAGCGGTG CACCGTGCTG TAGTGAGTGT GTGTCCAGGA TCCGCTTGAG
251 CAGGCGAGAT CGCCGAGGCA ACCCCAGTAG AAAAAGAAAA GAGGGGAAGT
301 AAGGCCGAGG CAAAGTGAAA GTAAAAGAGA TCCTCTGAGA AGAGGAACAG
351 GGGGCAATAA AATTGGCGCG AGCGCGTCAG GACTTAGGGG AAGAGAATTG
401 GATGAGCTGG AAAAGATTAG GTTACGGCCC TCCGGAAAGA AAAAATACCA
451 GCTAAAACAT GTGATATGGG TAAGCAAGGA ACTAGATAGA TTTGGCCTAC
501 ATGAAAAGTT GTTAGAAACC AAGGAAGGAT GCGAAAAAAT TCTTAGCGTA
551 CTCTTTCCTC TAGTTCCTAC AGGGTCAGAA AATTTAATTT CGCTGTACAA
601 CACCTGCTGT TGCATTTGGT GCGTACATGC GAAAGTGAAA GTAGCAGATA
651 CAGAAGAGGC AAAAGAGAAA GTAATACAAT GCTACCATCT AGTGGTTGAA
701 AAACAGAATG CAGCCTCAGA AAAAGAAAAA GGAGCAACAG TGACACCTAG
751 TGGCCACTCA ARAAATTACC CCATTCAGAT AGTAAATCAA ACCCCAGTAC

The still missing region of the total sequence of the integrase up to the 3′-LTR was amplified with the following primer pairs, the primer 1270 being discarded on account of the sequence of the 5′ LTR region (prior amplificate):

1. PCR:

(Seq. ID No. 13 and 14)

1246 CCT ATT CAT GGC CAG GTA

1270 GAT TTT TCT CTA CTC TCA CTA

2. Nested PCR:

(Seq. ID No. 15 and 16)

1196 AGT GAA AAG GTA GCC ACA GTC

12710 GAT TTT TCT CTA CTC TCA CTA

The platinum-Taq DNA polymerase (Gibco) was in each case used according to the following temperature program:

1) initial denaturation: 2 min. 95° C.,

2) amplification: 30 sec. 95° C., 30 sec. (47° C. 1.PCR; 51° C. 2. PCR), 360 sec. 68° C. (30 cycles). 1×enhancer (Gibco) was used in addition to the buffers indicated above.

The sequence according to Table 6 was obtained here:

TABLE 6
(SEQ ID NO: 21):
1    AGTGAAAAGG TAGCCACAGT CTGTTGGTGG GCTCAAATAG AGCACACCAC
51   AGGTGTACCC TATAACCCCC AGAGTCAGGG AGTAGTGGAA GCAAAGAATC
101  ATCATCTTAA GACAATCATA GAACAAGTTA GGGATCAAGC AGAAAAATTA
151  GAAACAGCAG TACAAATGGC AGTATTAATA CACAATTTTA AAAGAAAAGG
201  GGGGATAGGG GAGTATAGTC CAGGAGAAAG AATAGTAGAT ATCATAACCA
251  CAGACATTCT AACAACTAAA TTACAACAAA ATATTTCAAA AATTCAAAAT
301  TTTCGGGTTT ATTACAGAGA AGGAAGGGAT CAACAGTGGA AAGGACCAGC
351  AGAACTCATT TGGAAAGGAG AAGGCGCTGT GGTGATTAAA GAACGGACAG
401  ACTTAAAGGT GGTACCAAGA AGAAAAGCCA AAATCATCAG AGATTATGGA
451  AAAGCAGTGG ATAGTAATTC CCACATGGAG AGTAGAGAGG AATCAGCTTG
501  AGAAATGGAA TTCATTAGTA AAATATCATA AATATAGGGG AGAAAAATAC
551  CTAGAAAGAT GGGAACTATA CCACCATTTC CAATGCTCGG GGTGGTGGAC
601  ACACTCTAGA AAAGATGTTT ACTTTAAAGA TGGCTCAGTA ATAAGCATTA
651  CTGCCTTCTG GAATCTTACC CCAGAGAAAG GATGGTTGTC TCAATATGCA
701  GTTACAATAG AATATGTAAA AGAAAGCTAT TATACTTACA TAGACCCAGT
751  TACAGCAGAC AGAATGATTC ATTGGGAATA TTTCCCATGT TTTACAGCCC
801  AGGCTGTGAG AAAAGTACTG TTTGGAGAAA GACTAATAGC TTGCTACAGC
851  CCCTGGGGAC ACAAAGGACA GGTAGGGACT CTACAATTCC TGGCTTTGCA
901  AGCTTACCTT CAGTATTGTA AACATGGCAG AAAGAGCACC AGAAGTGCCG
951  GAAGGGGCAG GAGAGATACC TCTAGAACAG TGGCTAGAAA GATCATTAGA
1001 ACAACTCAAC AGAGAGGCCC GGTTACACTT CCACCCAGAG TTCCTTTTCC
1051 GTCTTTGGAA CACTTGTGTA GAACATTGGC ATGATAGACA CCAGAGGAGC
1101 CTGGAGTATG CAAAATACAG ATATCTTTTG TTGGTGCATA AGGCCATGTT
1151 TACCCATATG CAACAGGGAT GCCCATGTAG AAATGGGCAC CCAAGAGGAC
1201 CTCCTCCTCC AGGATTGGCC TAATTTCTGT CTTGCAGATG GAACAGCCAC
1251 CTGAGGACGA GGCTCCACAG AGAGAACCTT ATAATGAATG GCTGATAGAT
1301 ACCTTGGCAG AAATCCAGGA AGAAGCTTTG AAGCATTTTG ATAGGCGCTT

The total sequence which results from the sum of the sequences according to Tables 2 to 6 is shown in Table 7:

TABLE 7
(SEQ ID NO: 22):
1    TRDCTAGAGA TCCCTCAGAT TTGTGCCAGA CTTCTGATAT CTAGTGAGAG
51   TAGAGAAAAA TCTCCAGCAG TGGCGCCCGA ACAGGGACTT GACGAAGAGC
101  CAAGTCATTC CCACCTGTGA GGGACAGCGG CGGCAGCCGG CCGGACCGAC
151  CCACCCGGTG AAGTGAGTTA ACCAAGGAGC CCCGACGCGC AGGACACAAG
201  GTAAGCGGTG CACCGTGCTG TAGTGAGTGT GTGTCCAGGA TCCGCTTGAG
251  CAGGCGAGAT CGCCGAGGCA ACCCCAGTAG AAAAAGAAAA GAGGGGAAGT
301  AAGGCCGAGG CAAAGTGAAA GTAAAAGAGA TCCTCTGAGA AGAGGAACAG
351  GGGGCAATAA AATTGGCGCG AGCGCGTCAG GACTTAGGGG AAGAGAATTG
401  GATGAGCTGG AAAAGATTAG GTTACGGCCC TCCGGAAAGA AAAAATACCA
451  GCTAAAACAT GTGATATGGG TAAGCAAGGA ACTAGATAGA TTTGGCCTAC
501  ATGAAAAGTT GTTAGAAACC AAGGAAGGAT GCGAAAAAAT TCTTAGCGTA
551  CTCTTTCCTC TAGTTCCTAC AGGGTCAGAA AATTTAATTT CGCTGTACAA
601  CACCTGCTGT TGCATTTGGT GCGTACATGC GAAAGTGAAA GTAGCAGATA
651  CAGAAGAGGC AAAAGAGAAA GTAAAACAAT GCTACCATCT AGTGGTTGAA
701  AAACAGAATG CAGCCTCAGA AAAAGAAAAA GGAGCAACAG TGACACCTAG
751  TGGCCACTCA AGAAATTACC CCATTCAGAT AGTAAATCAA ACCCCAGTAC
801  ACCAGGGAAT TTCTCCCAGA ACACTGAATG CTTGGGTAAA ATGTATAGAG
851  GAGAAGAAAT TCAGCCCAGA AATAGTGCCT ATGTTCATAG CTTTGTCAGA
901  AGGATGCCTC CCATACGACC TCAACGGCAT GCTCAATGCC ATTGGGGACC
951  ATCAGGGAGC TCTCCAAATA GTGAAAGATG TCATCAATGA CGAAGCTGCA
1001 GACTGGGATC TTAGACATCC TCAGATGGGG CCTATGCCCC AAGGGGTGCT
1051 AAGAAACCCA ACAGGGAGTG ACATAGCAGG AACCACCAGC AGCATAGAAG
1101 AACAAATTGA ATGGACAACT AGGCAGCAAG ATCAGGTAAA TGTAGGAGGA
1151 ATTTACAAAC AATGGATAGT TCTGGGATTG CAAAAATGTG TGAGCATGTA

In 3 reading frames, the nucleotide sequence was converted into amino acid sequences, after which the amino acid sequences of GAG (Table 8), POL (Table 9) and ENV (Table 10) were identified by homology comparisons.

TABLE 8
GAG (SEQ ID NO: 23):
1   IGASASGLRG RELD'LEKIR LRDSGKKKYQ LKHVIWVSKE LDRFGLHLKL
51  LETKEGCEKI LSVLFPLVPT GSENLISLYN TCCCIWCVHA KVKVADTEEA
101 KEKVKQCYHL VVEKQNAASE KEKGATVTPS GHSRNYPIQI VNQTPVHQGI
151 SPRTLNAWVK CIEEKKFSPE IVPMFIALSE GCLDYDLNGM LNAIGDHQGA
201 LQIVKDVIND EAADWDLRHP QMGPMPQGVL RNPTGSDIAG TTSSIEEQIE
251 WTTRQQDQVN VGGIYKQWIV LGLQKCVSMY NPVNILDIKQ GPKEPFKDYV
301 DRFYKALRAE RTDPQVKNWM TQTLLIQNAN PDCK.AILKGL GMNPTLEEML
351 LACQGVGGPK YKAQMMAEAM QEVQGKIM.MQ ASGGPPRGPP RQPPRNPRCP
401 NCGKFGHVLR DCRAPRKRGC FKCGDPGHLM RNCPKMVNFL GNAPWGSGKP
451 RNFPAVPLTP TAPPMPGLED PAEKMLLDYM KKGQQMKAER EAKREKDKGP
501 YEAAYNSLSS LFGTDQLQ

TABLE 9
POL (SEQ ID NO: 24):
1   FFRECSLGQW QTQELSCRAT DPNGTPDARI RGPSREDATG LHELGATDEG
51  REGSQTGEGQ RPLRGGLQLP QFSLWNRPTT VVEIEGQKVE ALLDTGADDT
101 VIKDLQLTGN WKPQIIGGIG GAIRVKQYFN CKITVAGKST HAJVLVGPTP
151 VNIIGRNVLK KLGCTLNFPI SKIETVKVTL KPGTDGPRIK QWPLSKEKIL
201 ALQEICNQME KEGKISRIGP ENPYNTPVFC IKKKDGASWR KLVDFRQLNK
251 VTQDFCEVQL GIPHPGGLKQ CFQITVLDIG GAYFSCPLDE CFRKYTAFTI
301 PSVNNQGPGI RYQYNVLPQG WKGSPAIFQA TADKILKTFK EEYPEVLIYQ
351 YMDDLFVGSD LNATEHNKMI NKLREHLRFW GLETPDKKGQ KEPPFEWMGY
901 VLHPKKWTVQ KTQLPEKEQW TVNDIQKLVG KLNWASQIYS GIKTKELCKL
451 IRGAKPLDEI VEWTREAELE YEENKIIVQE EVHGVYYQPFE KPLMAKVQKL

TABLE 10
ENV (SEQ ID NO: 25):
1   QWVTVYYGTP KWHPARTHLF CATDNNSFWV TTSCVPSLLH YEEQHIPNIT
51  ENFTGPITEN EVIRQAWGAI SSMIDAVLKP CVKLTPYCVK MKCTKGDTDT
101 TERTTSTTSS WSTSTPTSTP MTPNTTGLDI DSNNTEPTTQ ENRICKFNTT
151 GLCRDCRLEI EENFRYQDIT CRNSSEDTEE CYMTHCNSSV ITQDCNKAST
201 DKMTFRLCAP PGYVLLRCRE KLNQTKLCGN ITAVQCTDPM PATISTMFGF
251 NGTKHDYDEL ILTNPQKINE FHDHKYVYRV DKKWKLQVVC RRKGNRSIIS
301 TPSATGLLFY HGLEPGKNLK KGMCQLKGLW GKAMHQLSEE LRKINGSIYR
351 KWNETAGCRK LNKQNGTGCS LKTIEVSEYT TEGDPGAETI MLLCGGEYFF
401 CNWTKIWKTW NNQTSNVWYP WMSCNIRQIV DDWHKVGKKI YMPPASGFNN
451 EIRCTNDVTE MFFEVQKKEE NKYLIKFIPQ DEIQNQYTAV GAHYKLVKVD
501 PIGFAPTDVH RYHLPDVKQK RGAVLLGMLC LLGLAGSAMG SVAIALTVQS
551 QALLNGIVEQ QKVLLSLIDQ HSELLKLTIW GVKNLQARLT ALEEYVADQS
641 RLAVWGCSFS QVC HTNVKWP NDSIVPNWTS ETWLEWDKRV TAITTTNMTID
651 LQRAYELEQK NMFELQKLGD LTSWASWFDL TWWFKYIKIG ILIIVIIGL
701 RILACLWSVL GRFRQGYRPL PYVFKGDYHR PHNLKQPDKE RGEEQDREKQ
751 NISSENYRPG SGRAWSKEQV ETWWKESRLY IWLKSTQAVI EYGWQELKAA
801 GAEIYKILQS AAQRLWSGGH QLGLSCIRRA TAFGRGVRNI PRRIRQGAEV
851 LLN

EXAMPLE 4

Determination of the Phylogenetic Position of SIM27

Selection of the sequences:

From the HIV WWW server of the LANL (Los Alamos National Laboratory, hiv-web.lanl.gov), 31 HIV and SIV sequences were selected which all comprised complete SIV genomes and representatives of the various HIV-1 and HIV-2 subtypes. The following sequences according to Table 11 were taken into consideration.

TABLE 11
Genbank
Accession No.: Name:
AF075269       SIV-1′hoesti
AF077017       SIV-SMM, PGM
L06042         SIV-SYKES
M27470         SIV-Mandrill, MNDGB1
L40990         SIV-VERVET, REV
M29975         SIV-VERVET, AGM155
M30931         SIV-VERVET, AGM3
X07805         SIV-VERVET, AGMTY6
M66437         SIV-GRIVET, AGMG77A
U04005         SIV-SABAEUS, AGMSAB1
AF103818       SIV-CPZ-US
U42720         SIV-CPZ, CPZANT
X52154         SIV-CPZ, CPZGAB
U58991         SIV-TANTALUS, TAN1
U72748         SIV, SME543
Y00277         SIV-D, MAC250
M32741         SIV-D, MNE
M33262         SIV-D, MM239
L09213         SIV-D, SMM-PBJ-6P9
M80194         SIV-D, SMM9
M83293         IV-D, STM
U51190         HIV1-A, 92ug037
AF110967       HIV1-C, 96bw05.02
M27323         HIV1-D, NDK
AF005494       HIV1-F, 93br020.1
AF005496       HIV1-H, 90cr056
AJ006022       HIV1-N, YBF30
L20587         HIV1-O, ANT70C
L20571         HIV1-O, MVP5180
D00835         HIV2-A, CAM2
M30895         HIV2-A, GH1
U27200         HIV2-B, EHO
L07625         HIV2-B, UC1

With the aid of the Genbank accession numbers of these sequences, the actual sequence entries were extracted from the gene database “Genbank”. With the aid of annotation, the genes env, gag and pol were extracted from these sequences and translated into the amino acid sequence. For the translation, only those sequences were used which were annotated as functional. Pseudogenes and genome sections not annotated as one of the 3 genes were not taken into consideration.

In addition, the sequence of the genome of SIM27 was compared with the actual gene database “Genbank” in order not to overlook an SIV partial sequence having a high relationship to SIM27. 2 partial sequences of SIVrcm (gag and pol) and a pol partial sequence of Mandrillus leucophaeus (Clewley JP et al., J. Virol. 1998; 72: 10305-10309) were identified as additionally relevant here:

RCM-GAG  SIV, RCM gag
RCM-POL  SIV, RCM pol
CLEW-POL SIV, Drill, Clewley

In total, 4 data sets were obtained in this way: 3 protein data sets (env, gag and pol), and one from genomic sequences (GENOME).

Alignment:

The above sequences were aligned together with the corresponding SIM27 sequences using CLUSTALW (Version 1.74) with standard settings (Thompson J. D et al., Nucleic Acids Res. 22: 4673-4680 (1994)). The sequence alignments thus obtained were then checked manually.

The published pol partial sequence of drill monkeys (Clewley et al.), and the pol partial sequence of the RCM monkey was added once more each to the pol sequence alignment in analyses which were separate in each case. The same was carried out for the GAG partial sequence of the RCM monkeys for the gag alignment.

For the addition of the individual sequences to the alignments, the profile alignment option of CLUSTALW 1.74 was used with standard settings.

3 further protein data sets with small partial sequences RCM-GAG, RCM-POL and DRILL-POL thus resulted. Each of these data sets was considered only with respect to the region of the respective partial sequence.

Phylogenetic Analyses

Using the above seven alignments (GENOME (FIG. 1 ), GAG (FIG. 2 ), RCM-GAG (FIG. 3 ), POL (FIG. 4 ), RCM-POL (FIG. 5 ), DRILL-POL (FIG. 6 ), ENV (FIG. 7 )), phylogenetic family trees were then independently set up. For this, the neighbor-joining method, as is implemented in CLUSTALW 1.74, was used in 1000 boot strap analyses. To calculate the trees, the standard settings were used, only all alignment gaps with holes were ignored, and the correction for multiple mutations was switched on.

EXAMPLE 5

Detection of the Diagnostic Relevance in the Western Blot

According to known methods of molecular biology (Current Protocols in Molecular Biology, Wiley Interscience, 1994), the region of env containing the cysteine loop was stabily expressed either as a fusion with the maltose-binding protein (pMAL-New England Biolabs) or as a fusion with β-Gal (Knapp et al., Biotechniques, Vol. 8, No. 3, 1990). The proteins were blotted on nitrocellulose, incubated overnight with the sera in a dilution of 1:100 in TBS containing 5% skimmed milk (150 mM NaCl, 50 mM tris pH 8.0), washed with TBS and incubated with anti-human IgG-AP (Sigma A064) and anti-monkey IgG-AP (Sigma A1929) for 2 h in a dilution of 1:1000 and stained according to the manufacturer's instructions by means of Nitrotetrazolium Blue (Sigma N-6878) and 5-bromo-4-chloroindolyl phosphate.p-toluidine (Bachem M105). The results shown in Table 9 were obtained (FIG. 9 ).

TABLE 9
		Anti-HIV1		Anti-SIV-
	Anti-HIV1	-subtype	Anti-HIV2	drill 7
Protein/serum	serum	O serum	serum	serum
PMAL-HIV1env	+ + +	+ +	−	−
PSEM-HIV1-	+ +	+ +	−	−
subtype-O-env
pMAL-HIV2-env	−	−	+ + +	−
pMAL-SIM27-	−	−	−	+ + +
env
pMAL	−	−	−	−
PSEM	−	−	−	−

It was surprisingly seen here that the env region of SIM27 does not react with anti-HIV-1, anti-HIV-1 subtype O and anti-HIV2 sera and at the same time antibodies from SIM27, which react strongly with SIM27-env, could not be detected by the use of HIV-1-env, HIV-1-subtype O env and HIV2-env. It is therefore to be assumed from this that in the case in which SIM27 or a variant with comparable serological properties ought to complete the transition into the human population, the detection of antibodies against SIM27 in human sera is not possible with the tests currently employed, but rather SIM27-env, or antigens derived therefrom having comparable immunological properties, have to be employed.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 Phylogenetic investigation of the sequences of Table 11 including the total genome of SIM27 as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 2 Phylogenetic investigation of the GAG proteins extracted from the sequences of Table 11 including the GAG protein of SIM27 (Table 8) as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 3 Phylogenetic investigation of the GAG proteins extracted from the sequences of Table 11 including the GAG protein of SIM27 (Table 8) and the GAG partial sequence of SIVrcm as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 4 Phylogenetic investigation of the POL proteins extracted from the sequences of Table 11 including the POL protein of SIM27 (Table 9) as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 5 Phylogenetic investigation of the POL proteins extracted from the sequences of Table 11 including the POL protein of SIM27 (Table 9) and the POL partial sequence of SIVrcm as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 6 Phylogenetic investigation of the POL proteins extracted from the sequences of Table 11 including the POL protein of SIM27 (Table 9) and the POL partial sequence as published by Clewley (Clewley JP et al., J. Virol. 1998; 72: 10305-10309) and as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 7 Phylogenetic investigation of the ENV proteins extracted from the sequences of Table 11 including the ENV protein of SIM27 (Table 10) as described in Example 4 by the multiple alignment and the neighbor-joining method of ClustalW Version 1.74

FIG. 8 General survey of the individual PCR amplifications which lead to the complete genomic nucleic acid sequence of SIM27.

FIG. 9 Western blot, as described in Example 5.

ABBREVIATIONS

HIV:  Human immunodeficiency virus
SIV:  Simian (monkey) immunodeficiency virus
HTLV: Human T-lymphoma virus
STLV: Simian T-lymphoma virus
p:    Protein
gp:   Glycoprotein
pol:  Gene of the enzymes of HIV or SIV, designated
      according to the polymerase
gag:  Gene of the core proteins of HIV or SIV
env:  Gene of the surface glycoproteins/glyco-
      proteins of HIV or SIV
IN:   Integrase
RT:   Reverse transcriptase
PR:   Protease

57 1 20 DNA Unknown misc_feature ()..() primer, non-genomic DNA 1gccatgtgtc caaaatgtca 20 2 20 DNA Unknown misc_feature ()..() primer, non-genomic DNA 2cttctctgta gtagactcta 20 3 18 DNA Unknown misc_feature ()..() primer, non-genomic DNA 3tagtagcagt ccmyrkwg 18 4 20 DNA Unknown misc_feature ()..() primer, non-genomic DNA 4tctctaattt gtcctatgat 20 5 19 DNA Unknown misc_feature ()..() primer, non-genomic DNA 5atgcccattg gatgaggac 19 6 21 DNA Unknown misc_feature ()..() primer, non-genomic DNA 6gactgtggct accttttcac t 21 7 18 DNA Unknown misc_feature ()..() primer, non-genomic DNA 7catcggtgaa taatcagg 18 8 19 DNA Unknown misc_feature ()..() primer, non-genomic DNA 8ggtattactt ctgcctcta 19 9 20 DNA Unknown misc_feature ()..() primer, non-genomic DNA 9ctcaataaag cttgccttga 20 10 19 DNA Unknown misc_feature ()..() primer, non-genomic DNA 10gtcctcatcc aatgggcat 19 11 19 DNA Unknown misc_feature ()..() primer, non-genomic DNA 11trdctagaga tccctcaga 19 12 21 DNA Unknown misc_feature ()..() primer, non-genomic DNA 12ccaatactgt gatctgttca c 21 13 18 DNA Unknown misc_feature ()..() primer, non-genomic DNA 13cctattcatg gccaggta 18 14 21 DNA Unknown misc_feature ()..() primer, non-genomic DNA 14gatttttctc tactctcact a 21 15 21 DNA Unknown misc_feature ()..() primer, non-genomic DNA 15agtgaaaagg tagccacagt c 21 16 21 DNA Unknown misc_feature ()..() primer, non-genomic DNA 16gatttttctc tactctcact a 21 17 279 DNA SIV - viral 17agtagcagtc catgtagcca gtggatacct agaggcagaa gtaataccag cagagacagg 60aaaagagaca gcacatttcc tgttaaagtt agcaggcagg tggcctgtaa aacatttaca 120cactgacaat ggccccaact ttgtcagtga aaaggtagcc acagtctgtt ggtgggctca 180aatagagcac accacaggtg taccctataa cccccagagt cagggagtag tggaagcaaa 240gaatcatcat cttaagacaa tcataggaca aattagaga 279 18 195 DNA SIV - viral Unsure (175)..(175) “n” can be any base 18gggattccgc anccggcagg tctaaaacaa tgtgaacaga tcacagtatt ggatatagga 60gatgcctatt tttcatgccc attggatgag gactttagaa agtatactgc attcaccatt 120ccatcggtga ataatcaggg gcccaggaat cagataccag tataatgtcc tcccncaggg 180ntggaagggg tcccc 195 19 1551 DNA SIV - viral 19catcggtgaa taatcagggc ccaggaatca gataccagta taatgtcctc ccacagggat 60ggaaaggctc tccagcaatt tttcaggcaa cagctgataa aatcttgaaa acattcaaag 120aagaatacca gaggtattaa tttatcagta tatggatgat ctgttcgtgg gaagtgactt 180aaatgccact gaacataaca aaatgataaa caagttgaga gagcatctga gattctgggg 240gctcgagacc ccagataaga agtttcaaaa ggaacctcct tttgaatgga tgggatatgt 300gctacaccca aagaaatgga cagtgcagaa aatacaacta ccagaaaaag agcaatggac 360agtgaatgat attcagaaat tggtaggaaa acttaattgg gcaagtcaga tatattccgg 420aattaaaaca aaagagctct gtaaattgat cagaggagca aaacctctag atgaaatagt 480agaatggaca agagaagcag aattagagta tgaagagaat aagataatag tgcaggagga 540ggtgcatgga gtgtactatc agccagaaaa accactgatg gcaaaagtac aaaagttgac 600acaaggacag tggagttatc aaatagagca agaagaaaac aaacctctca aggcaggaaa 660atatgccagg acaaagaatg cccacacaaa tgagttaagg acacttgcag ggttagtaca 720aaaaatagcc aaggaatgca tagtaatctg gggaagattg ccaaaatttt acctcccctt 780ggagagagaa gtatgggatc aatggtggca tgattattgg caggtaacat ggatcccaga 840gtgggaattc atctcaacac caccattgat aaggctatgg tacaacctcc tgaaagaacc 900aattccagga gaagatgtat actatgtaga tggggcagct aacagaaatt ctaaagaagg 960caaggcagga tactatacag caaggggcaa aagtaaggta atagctttag aaaatacaac 1020caatcagaag gcagagctga aggcaataga attagcccta aaagattcag gaccaagagt 1080aaacatagta acagattcac agtatgcatt aggcatactc acagcatccc cagatcagtc 1140agataacccc atagttaggg aaataattaa cctcatgata gccaaggaag cagtctacct 1200gtcatgggta ccagcccaca agggtatagg aggtaacgaa caaatagaca aattagtaag 1260ccaaggaatt aggcaagtac tattcctgga aggaatagac agagctcagg aagaacacga 1320caaatatcat aacaactgga gagctttagc tcaggaattc agcatacctc ctatagtggc 1380aaaagagata gttgcacaat gcccaaaatg ccagataaaa ggggaaccta ttcatggcca 1440ggtagatgca agtcctggga catggcaaat ggattgcacc catctagaag gaaaggtcat 1500catagtggca gtccatgtag ccagtggata cctagaggca gaagtaatac c 1551 20 2500 DNA SIV - viral 20trdctagaga tccctcagat ttgtgccaga cttctgatat ctagtgagag tagagaaaaa 60tctccagcag tggcgcccga acagggactt gacgaagagc caagtcattc ccacctgtga 120gggacagcgg cggcagccrg ccggaccgac ccacccggtg aagtgagtta accaaggagc 180cccgacgcgc aggacacaag gtaagcggtg caccgtgctg tagtgagtgt gtgtccagga 240tccgcttgag caggcgagat cgccgaggca accccagtag aaaaagaaaa gaggggaagt 300aaggccgagg caaagtgaaa gtaaaagaga tcctctgaga agaggaacag ggggcaataa 360aattggcgcg agcgcgtcag gacttagggg aagagaattg gatgagctgg aaaagattag 420gttacggccc tccggaaaga aaaaatacca gctaaaacat gtgatatggg taagcaagga 480actagataga tttggcctac atgaaaagtt gttagaaacc aaggaaggat gcgaaaaaat 540tcttagcgta ctctttcctc tagttcctac agggtcagaa aatttaattt cgctgtacaa 600cacctgctgt tgcatttggt gcgtacatgc gaaagtgaaa gtagcagata cagaagaggc 660aaaagagaaa gtaaracaat gctaccatct agtggttgaa aaacagaatg cagcctcaga 720aaaagaaaaa ggagcaacag tgacacctag tggccactca araaattacc ccattcagat 780agtaaatcaa accccagtac accagggaat ttctcccaga acactgaatg cttgggtaaa 840atgtatagag gagaagaaat tcagcccaga aatagtgcct atgttcatag ctttgtcaga 900aggatgcctc ccatacgacc tcaacggcat gctcaatgcc attggggacc atcagggagc 960tctccaaata gtgaaagatg tcatcaatga cgaagctgca gactgggatc ttagacatcc 1020tcagatgggg cctatgcccc aaggggtgct aagaaaccca acagggagtg acatagcagg 1080aaccaccagc agcatagaag aacaaattga atggacaact aggcagcaag atcaggtaaa 1140tgtaggagga atttacaaac aatggatagt tctgggattg caaaaatgtg tgagcatgta 1200caatccagtg aatattctag atataaaaca gggaccaaaa gaacccttta aggactatgt 1260ggatcgattt tacaaagctc tgcgggcgga gcgaacagat ccacaagtga aaaactggat 1320gacgcagaca ttgctcatcc agaatgcaaa cccagattgt aaagccattc ttaagggatt 1380aggcatgaac cccaccttgg aagaaatgtt attggcatgt caaggagtag ggggaccaaa 1440gtataaagct caaatgatgg cagaagcaat gcaggaggtg caaggaaaaa ttatgatgca 1500agcctcggga ggaccaccgc ggggtccccc aaggcagcca cccagaaatc ctagatgccc 1560caactgtgga aagtttggac atgtactgag agactgtaga gccccaagaa agcgaggatg 1620cttcaagtgt ggagatccag gacatctgat gagaaactgc ccaaagatgg tgaatttttt 1680agggaatgct ccytggggca gtggcaaacc caggaacttt cctgccgtgc cactgacccc 1740aacggcaccc ccgatgccag gattagagga yccagcagag argatgctrc tggattacat 1800gaagaagggg caacagatga aggcagagag ggaagccaaa cgggagaagg acaaaggccc 1860ttacgaggcg gcttacaact ccctcagttc tctctttgga acagaccaac tacagtagta 1920gagatagagg ggcaaaaagt ggaggcccta ctagatacag gagcagatga cacagtaatc 1980aaagatttac aattaacagg caattggaaa ccacaaatca taggaggaat tggaggagca 2040attagggtaa agcaatattt caattgtaaa ataacagtgg caggtaaaag cactcatgct 2100tcagtactag tgggccccac tcctgtaaat attataggta gaaatgtact taaaaagtta 2160ggatgtactt tgaactttcc tattagtaar atagaaacag taaaggtaac actaaaacca 2220ggaactgatg gaccaagaat caaacagtgg ccactgtcta aagaaaagat tttagcctta 2280caagaaatat gcaatcagat ggaaaaagaa ggcaaaatct ctagaatagg tccagaaaat 2340ccttacaaca caccagtgtt ttgtataaaa aagaaagatg gagccagctg gagaaaactg 2400gtagatttta gacaattgaa taaagtgaca caggatttct ttgaggtgca gctaggaatc 2460ccacatcctg gaggtctaaa acaatgtgaa cagatcacag 2500 21 5428 DNA SIV - viral 21agtgaaaagg tagccacagt ctgttggtgg gctcaaatag agcacaccac aggtgtaccc 60tataaccccc agagtcaggg agtagtggaa gcaaagaatc atcatcttaa gacaatcata 120gaacaagtta gggatcaagc agaaaaatta gaaacagcag tacaaatggc agtattaata 180cacaatttta aaagaaaagg ggggataggg gagtatagtc caggagaaag aatagtagat 240atcataacca cagacattct aacaactaaa ttacaacaaa atatttcaaa aattcaaaat 300tttcgggttt attacagaga aggaagggat caacagtgga aaggaccagc agaactcatt 360tggaaaggag aaggcgctgt ggtgattaaa gaagggacag acttaaaggt ggtaccaaga 420agaaaagcca aaatcatcag agattatgga aaagcagtgg atagtaattc ccacatggag 480agtagagagg aatcagcttg agaaatggaa ttcattagta aaatatcata aatatagggg 540agaaaaatac ctagaaagat gggaactata ccaccatttc caatgctcgg ggtggtggac 600acactctaga aaagatgttt actttaaaga tggctcagta ataagcatta ctgccttctg 660gaatcttacc ccagagaaag gatggttgtc tcaatatgca gttacaatag aatatgtaaa 720agaaagctat tatacttaca tagacccagt tacagcagac agaatgattc attgggaata 780tttcccatgt tttacagccc aggctgtgag aaaagtactg tttggagaaa gactaatagc 840ttgctacagc ccctggggac acaaaggaca ggtagggact ctacaattcc tggctttgca 900agcttacctt cagtattgta aacatggcag aaagagcacc agaagtgccg gaaggggcag 960gagagatacc tctagaacag tggctagaaa gatcattaga acaactcaac agagaggccc 1020ggttacactt ccacccagag ttccttttcc gtctttggaa cacttgtgta gaacattggc 1080atgatagaca ccagaggagc ctggagtatg caaaatacag atatcttttg ttggtgcata 1140aggccatgtt tacccatatg caacagggat gcccatgtag aaatgggcac ccaagaggac 1200ctcctcctcc aggattggcc taatttctgt cttgcagatg gaacagccac ctgaggacga 1260ggctccacag agagaacctt ataatgaatg gctgatagat accttggcag aaatccagga 1320agaagctttg aagcattttg ataggcgctt gctacatgca gtaggctcat gggtgtatga 1380gcaacaggga gacaccttag aaggtgtcca aaagctaata actattctac aaagagcttt 1440gtttttgcac ttcaggcatg gatgcaggga aagccgcatt ggacaagcag gagggaaata 1500taattccctc agatcctttc caaggccaga caaccccttg taataaatgc tattgtaaaa 1560gatgttgcta tcactgccag ttatgcttct tgcagaaagc cttagggata cattatcatg 1620tctacagagt caggagacct cgacagagat ttttgggcga agtaccacca catagtgcag 1680caactgtgga aaggtaagta aaaagtaagt agacatgctt agatatatag ttttaggaat 1740agtcatagga ttagggatag gacaccaatg ggttacagtg tattatggaa cacctaaatg 1800gcacccagct aggacacatc tcttttgtgc aacagataat aattcctttt gggtcacaac 1860aagttgtgtg cccagcctat tgcactatga agaacaacac attcccaaca taacagaaaa 1920cttcacaggc cccataacag agaatgaagt aataagacaa gcatggggag ctatctcttc 1980catgatagat gcagtcttaa aaccctgtgt aaagctgaca ccatattgtg tcaagatgaa 2040atgcacaaag ggagatactg atactacaga aaggacaaca tcaaccactt cctcttggtc 2100cacatccacc ccaacctcta cccctatgac tcccaatacc actggattag atatagactc 2160aaacaataca gaacccacaa cacaagagaa tcggatatgt aaatttaata ctacaggatt 2220atgtagagac tgcagattgg aaatagaaga aaacttcaga tatcaggata taacatgtag 2280aaatagtagt gaagatactg aagagtgcta tatgacacat tgtaactcat cagtaataac 2340acaggattgc aataaggcat caacagataa aatgactttt aggttgtgtg caccaccagg 2400atatgtcctg ttgagatgta gagaaaagct aaaccaaacc aaattgtgtg gcaatattac 2460agcagtgcaa tgcactgacc caatgcctgc aactatatcc actatgtttg gatttaatgg 2520gaccaaacat gactatgatg agctaatttt aacaaaccct caaaagataa atgagtttca 2580tgatcacaag tatgtatata gagttgataa aaaatggaag ctacaggtag tatgtagaag 2640aaaagggaat agatcaataa tatcaacgcc aagtgctacg ggcttattgt tctatcatgg 2700gctagaacca gggaaaaatt taaaaaaggg gatgtgccag ctgaagggat tatggggaaa 2760ggccatgcac caactatcag aggaacttag aaagataaat ggaagtattt atagaaaatg 2820gaatgagaca gcaggctgca gaaagctaaa caaacagaac ggtacaggtt gctcattgaa 2880aacaatagaa gttagtgagt acaccacgga gggcgatccg ggggcagaga caattatgct 2940tctttgtgga ggtgagtatt tcttttgtaa ttggacaaag atttggaaga catggaataa 3000ccagacgtca aatgtctggt atccttggat gtcatgcaat attagacaaa ttgtagatga 3060ttggcataaa gtagggaaaa aaatttatat gcctcctgca agtggattta acaatgagat 3120aaggtgtact aatgatgtca cggaaatgtt ctttgaggtt cagaagaagg aagagaataa 3180atatttaata aagtttatac ctcaagatga gatacaaaat cagtatacag cagtaggagc 3240acattataaa ttggtgaaag tggatcctat agggttcgca cccacagatg tgcatagata 3300ccatctacca gatgtaaagc agaagagagg agcagtcttg cttggaatgc tcggcctctt 3360aggtttggca ggttccgcga tgggctcagt ggcgatagca ctgacggtcc agtcccaggc 3420tttattgaat gggattgtgg agcagcagaa ggttctgctg agcctgatag atcagcactc 3480cgagttatta aaactaacta tctggggtgt aaaaaatctt caggcccgcc tcacagcctt 3540ggaggaatac gtagcggacc aatcaagact ggcagtatgg ggatgctcat tctctcaagt 3600atgccacact aatgtaaagt ggcctaatga ttcaatagtt cctaactgga cctcggaaac 3660atggcttgaa tgggataaaa gagtgacagc aattacaaca aatatgacaa tagacttgca 3720gagggcatat gaattggaac aaaagaatat gtttgagctt caaaaattag gagatctcac 3780ctcctgggcc agctggttcg acctcacgtg gtggtttaaa tatattaaga taggaattct 3840tataataata gtgataatag gacttagaat attagcttgc ttatggtcag tattaggcag 3900gtttaggcag ggttaccgcc ctcttcctta tgtcttcaag ggagactatc accgacccca 3960caacctcaaa cagccagaca aagaaagagg agaagagcaa gacagagaaa aacagaacat 4020cagctcagag aattacaggc caggatctgg cagagcttgg agcaaagagc aagtagagac 4080ctggtggaag gagtccaggc tctacatttg gttgaagagc acacaagcag taattgaata 4140tgggtggcaa gagctcaaag cagcaggagc agaaatatat aaaatattac agagcgctgc 4200gcagaggcta tggagcggag ggcaccaact cggactatca tgtattagag cagctacagc 4260ctttggcaga ggagtcagaa acattcctag acgcatcaga caaggagcag aagtcttact 4320caactgagtt agacttaaga catcaacaag atgtaagcct ccccacagaa gaagaacagc 4380cttgggaaga ggaagaggag gtaggctttc cagtctaccc acgacagcct gtgcatgaag 4440ccacctataa agacttgata gacctgtccc actttttaaa agaaaagggg ggactggaag 4500ggatttggtg gtctaaaaga agagaagaaa tcttggatat atatgcacaa aatgaatggg 4560gaattatacc tgactggcag gcttacactt caggaccggg gatcaggtat ccaaaagcat 4620ttgggttcct gtttaaactg atcccagtgg cagttccacc ggaacaagag aacaatgaat 4680gcaataggct gctaaactct tctcagacag gaatccagga agatccatgg ggagaaaggc 4740tcatgtggaa gtttgactct gctcttgcct atactttcta tgctcccata aagaggccag 4800gagacttcaa gcatgtccaa agtcttagct atgaagctta taagaaggaa cctgactgct 4860gcaagaggaa gtggtggcgc ttctagccga ccacagaggg ttgctatggc gatacccttt 4920aaaactgcta actctggagg gactttccac tagtgcatgc gcactggact ggggactttc 4980caggatgacg ccgggtgggg gagtggtcag cccaatctgg ctgcatataa gcagctcgct 5040ttgcgcttgt attgagtctc tccctgagag gctaccagat tgagcctagg ttgttctctg 5100gtgagtcctt gaaggagtgc ctgcttgtag ccctgggcgg ttcgcaggcc cctggcttgt 5160agctctgggt agctcgtcag gtgttctgga aaggtcttgc taaggggacg cctttgcttg 5220gtcttggtag acctctagca gtctcagtgg ccaggaggct gtgggattga ctaccgcttg 5280cttgcctttg atgctcaata aagcttaccc gaattagaaa ggcattcaag tgtactcgct 5340cattttgtct ttggtagaaa ctctggttac tggagatccc tcagatttgt gccagacttc 5400tgatatctag tgagagtaga gaaaaatc 5428 22 9641 DNA SIV - viral 22trdctagaga tccctcagat ttgtgccaga cttctgatat ctagtgagag tagagaaaaa 60tctccagcag tggcgcccga acagggactt gacgaagagc caagtcattc ccacctgtga 120gggacagcgg cggcagccgg ccggaccgac ccacccggtg aagtgagtta accaaggagc 180cccgacgcgc aggacacaag gtaagcggtg caccgtgctg tagtgagtgt gtgtccagga 240tccgcttgag caggcgagat cgccgaggca accccagtag aaaaagaaaa gaggggaagt 300aaggccgagg caaagtgaaa gtaaaagaga tcctctgaga agaggaacag ggggcaataa 360aattggcgcg agcgcgtcag gacttagggg aagagaattg gatgagctgg aaaagattag 420gttacggccc tccggaaaga aaaaatacca gctaaaacat gtgatatggg taagcaagga 480actagataga tttggcctac atgaaaagtt gttagaaacc aaggaaggat gcgaaaaaat 540tcttagcgta ctctttcctc tagttcctac agggtcagaa aatttaattt cgctgtacaa 600cacctgctgt tgcatttggt gcgtacatgc gaaagtgaaa gtagcagata cagaagaggc 660aaaagagaaa gtaaaacaat gctaccatct agtggttgaa aaacagaatg cagcctcaga 720aaaagaaaaa ggagcaacag tgacacctag tggccactca agaaattacc ccattcagat 780agtaaatcaa accccagtac accagggaat ttctcccaga acactgaatg cttgggtaaa 840atgtatagag gagaagaaat tcagcccaga aatagtgcct atgttcatag ctttgtcaga 900aggatgcctc ccatacgacc tcaacggcat gctcaatgcc attggggacc atcagggagc 960tctccaaata gtgaaagatg tcatcaatga cgaagctgca gactgggatc ttagacatcc 1020tcagatgggg cctatgcccc aaggggtgct aagaaaccca acagggagtg acatagcagg 1080aaccaccagc agcatagaag aacaaattga atggacaact aggcagcaag atcaggtaaa 1140tgtaggagga atttacaaac aatggatagt tctgggattg caaaaatgtg tgagcatgta 1200caatccagtg aatattctag atataaaaca gggaccaaaa gaacccttta aggactatgt 1260ggatcgattt tacaaagctc tgcgggcgga gcgaacagat ccacaagtga aaaactggat 1320gacgcagaca ttgctcatcc agaatgcaaa cccagattgt aaagccattc ttaagggatt 1380aggcatgaac cccaccttgg aagaaatgtt attggcatgt caaggagtag ggggaccaaa 1440gtataaagct caaatgatgg cagaagcaat gcaggaggtg caaggaaaaa ttatgatgca 1500agcctcggga ggaccaccgc ggggtccccc aaggcagcca cccagaaatc ctagatgccc 1560caactgtgga aagtttggac atgtactgag agactgtaga gccccaagaa agcgaggatg 1620cttcaagtgt ggagatccag gacatctgat gagaaactgc ccaaagatgg tgaatttttt 1680agggaatgct ccctggggca gtggcaaacc caggaacttt cctgccgtgc cactgacccc 1740aacggcaccc ccgatgccag gattagagga cccagcagag aagatgctac tggattacat 1800gaagaagggg caacagatga aggcagagag ggaagccaaa cgggagaagg acaaaggccc 1860ttacgaggcg gcttacaact ccctcagttc tctctttgga acagaccaac tacagtagta 1920gagatagagg ggcaaaaagt ggaggcccta ctagatacag gagcagatga cacagtaatc 1980aaagatttac aattaacagg caattggaaa ccacaaatca taggaggaat tggaggagca 2040attagggtaa agcaatattt caattgtaaa ataacagtgg caggtaaaag cactcatgct 2100tcagtactag tgggccccac tcctgtaaat attataggta gaaatgtact taaaaagtta 2160ggatgtactt tgaactttcc tattagtaag atagaaacag taaaggtaac actaaaacca 2220ggaactgatg gaccaagaat caaacagtgg ccactgtcta aagaaaagat tttagcctta 2280caagaaatat gcaatcagat ggaaaaagaa ggcaaaatct ctagaatagg tccagaaaat 2340ccttacaaca caccagtgtt ttgtataaaa aagaaagatg gagccagctg gagaaaactg 2400gtagatttta gacaattgaa taaagtgaca caggatttct ttgaggtgca gctaggaatc 2460ccacatcctg gaggtctaaa acaatgtgaa cagatcacag tattggatat aggagatgcc 2520tatttttcat gcccattgga tgaggacttt agaaagtata ctgcattcac cattccatcg 2580gtgaataatc agggcccagg aatcagatac cagtataatg tcctcccaca gggatggaaa 2640ggctctccag caatttttca ggcaacagct gataaaatct tgaaaacatt caaagaagaa 2700tacccagagg tattaattta tcagtatatg gatgatctgt tcgtgggaag tgacttaaat 2760gccactgaac ataacaaaat gataaacaag ttgagagagc atctgagatt ctgggggctc 2820gagaccccag ataagaagtt tcaaaaggaa cctccttttg aatggatggg atatgtgcta 2880cacccaaaga aatggacagt gcagaaaata caactaccag aaaaagagca atggacagtg 2940aatgatattc agaaattggt aggaaaactt aattgggcaa gtcagatata ttccggaatt 3000aaaacaaaag agctctgtaa attgatcaga ggagcaaaac ctctagatga aatagtagaa 3060tggacaagag aagcagaatt agagtatgaa gagaataaga taatagtgca ggaggaggtg 3120catggagtgt actatcagcc agaaaaacca ctgatggcaa aagtacaaaa gttgacacaa 3180ggacagtgga gttatcaaat agagcaagaa gaaaacaaac ctctcaaggc aggaaaatat 3240gccaggacaa agaatgccca cacaaatgag ttaaggacac ttgcagggtt agtacaaaaa 3300atagccaagg aatgcatagt aatctgggga agattgccaa aattttacct ccccttggag 3360agagaagtat gggatcaatg gtggcatgat tattggcagg taacatggat cccagagtgg 3420gaattcatct caacaccacc attgataagg ctatggtaca acctcctgaa agaaccaatt 3480ccaggagaag atgtatacta tgtagatggg gcagctaaca gaaattctaa agaaggcaag 3540gcaggatact atacagcaag gggcaaaagt aaggtaatag ctttagaaaa tacaaccaat 3600cagaaggcag agctgaaggc aatagaatta gccctaaaag attcaggacc aagagtaaac 3660atagtaacag attcacagta tgcattaggc atactcacag catccccaga tcagtcagat 3720aaccccatag ttagggaaat aattaacctc atgatagcca aggaagcagt ctacctgtca 3780tgggtaccag cccacaaggg tataggaggt aacgaacaaa tagacaaatt agtaagccaa 3840ggaattaggc aagtactatt cctggaagga atagacagag ctcaggaaga acacgacaaa 3900tatcataaca actggagagc tttagctcag gaattcagca tacctcctat agtggcaaaa 3960gagatagttg cacaatgccc aaaatgccag ataaaagggg aacctattca tggccaggta 4020gatgcaagtc ctgggacatg gcaaatggat tgcacccatc tagaaggaaa ggtcatcata 4080gtggcagtcc atgtagccag tggataccta gaggcagaag taataccagc agagacagga 4140aaagagacag cacatttcct gttaaagtta gcaggcaggt ggcctgtaaa acatttacac 4200actgacaatg gccccaactt tgtcagtgaa aaggtagcca cagtctgttg gtgggctcaa 4260atagagcaca ccacaggtgt accctataac ccccagagtc agggagtagt ggaagcaaag 4320aatcatcatc ttaagacaat catagaacaa gttagggatc aagcagaaaa attagaaaca 4380gcagtacaaa tggcagtatt aatacacaat tttaaaagaa aaggggggat aggggagtat 4440agtccaggag aaagaatagt agatatcata accacagaca ttctaacaac taaattacaa 4500caaaatattt caaaaattca aaattttcgg gtttattaca gagaaggaag ggatcaacag 4560tggaaaggac cagcagaact catttggaaa ggagaaggcg ctgtggtgat taaagaaggg 4620acagacttaa aggtggtacc aagaagaaaa gccaaaatca tcagagatta tggaaaagca 4680gtggatagta attcccacat ggagagtaga gaggaatcag cttgagaaat ggaattcatt 4740agtaaaatat cataaatata ggggagaaaa atacctagaa agatgggaac tataccacca 4800tttccaatgc tcggggtggt ggacacactc tagaaaagat gtttacttta aagatggctc 4860agtaataagc attactgcct tctggaatct taccccagag aaaggatggt tgtctcaata 4920tgcagttaca atagaatatg taaaagaaag ctattatact tacatagacc cagttacagc 4980agacagaatg attcattggg aatatttccc atgttttaca gcccaggctg tgagaaaagt 5040actgtttgga gaaagactaa tagcttgcta cagcccctgg ggacacaaag gacaggtagg 5100gactctacaa ttcctggctt tgcaagctta ccttcagtat tgtaaacatg gcagaaagag 5160caccagaagt gccggaaggg gcaggagaga tacctctaga acagtggcta gaaagatcat 5220tagaacaact caacagagag gcccggttac acttccaccc agagttcctt ttccgtcttt 5280ggaacacttg tgtagaacat tggcatgata gacaccagag gagcctggag tatgcaaaat 5340acagatatct tttgttggtg cataaggcca tgtttaccca tatgcaacag ggatgcccat 5400gtagaaatgg gcacccaaga ggacctcctc ctccaggatt ggcctaattt ctgtcttgca 5460gatggaacag ccacctgagg acgaggctcc acagagagaa ccttataatg aatggctgat 5520agataccttg gcagaaatcc aggaagaagc tttgaagcat tttgataggc gcttgctaca 5580tgcagtaggc tcatgggtgt atgagcaaca gggagacacc ttagaaggtg tccaaaagct 5640aataactatt ctacaaagag ctttgttttt gcacttcagg catggatgca gggaaagccg 5700cattggacaa gcaggaggga aatataattc cctcagatcc tttccaaggc cagacaaccc 5760cttgtaataa atgctattgt aaaagatgtt gctatcactg ccagttatgc ttcttgcaga 5820aagccttagg gatacattat catgtctaca gagtcaggag acctcgacag agatttttgg 5880gcgaagtacc accacatagt gcagcaactg tggaaaggta agtaaaaagt aagtagacat 5940gcttagatat atagttttag gaatagtcat aggattaggg ataggacacc aatgggttac 6000agtgtattat ggaacaccta aatggcaccc agctaggaca catctctttt gtgcaacaga 6060taataattcc ttttgggtca caacaagttg tgtgcccagc ctattgcact atgaagaaca 6120acacattccc aacataacag aaaacttcac aggccccata acagagaatg aagtaataag 6180acaagcatgg ggagctatct cttccatgat agatgcagtc ttaaaaccct gtgtaaagct 6240gacaccatat tgtgtcaaga tgaaatgcac aaagggagat actgatacta cagaaaggac 6300aacatccacc acttcctctt ggtccacatc caccccaacc tctaccccta tgactcccaa 6360taccactgga ttagatatag actcaaacaa tacagaaccc acaacacaag agaatcggat 6420atgtaaattt aatactacag gattatgtag agactgcaga ttggaaatag aagaaaactt 6480cagatatcag gatataacat gtagaaatag tagtgaagat actgaagagt gctatatgac 6540acattgtaac tcatcagtaa taacacagga ttgcaataag gcatcaacag ataaaatgac 6600ttttaggttg tgtgcaccac caggatatgt cctgttgaga tgtagagaaa agctaaacca 6660aaccaaattg tgtggcaata ttacagcagt gcaatgcact gacccaatgc ctgcaactat 6720atccactatg tttggattta atgggaccaa acatgactat gatgagctaa ttttaacaaa 6780ccctcaaaag ataaatgagt ttcatgatca caagtatgta tatagagttg ataaaaaatg 6840gaagctacag gtagtatgta gaagaaaagg gaatagatca ataatatcaa cgccaagtgc 6900tacgggctta ttgttctatc atgggctaga accagggaaa aatttaaaaa aggggatgtg 6960ccagctgaag ggattatggg gaaaggccat gcaccaacta tcagaggaac ttagaaagat 7020aaatggaagt atttatagaa aatggaatga gacagcaggc tgcagaaagc taaacaaaca 7080gaacggtaca ggttgctcat tgaaaacaat agaagttagt gagtacacca cggagggcga 7140tccgggggca gagacaatta tgcttctttg tggaggtgag tatttctttt gtaattggac 7200aaagatttgg aagacatgga ataaccagac gtcaaatgtc tggtatcctt ggatgtcatg 7260caatattaga caaattgtag atgattggca taaagtaggg aaaaaaattt atatgcctcc 7320tgcaagtgga tttaacaatg agataaggtg tactaatgat gtcacggaaa tgttctttga 7380ggttcagaag aaggaagaga ataaatattt aataaagttt atacctcaag atgagataca 7440aaatcagtat acagcagtag gagcacatta taaattggtg aaagtggatc ctatagggtt 7500cgcacccaca gatgtgcata gataccatct accagatgta aagcagaaga gaggagcagt 7560cttgcttgga atgctcggcc tcttaggttt ggcaggttcc gcgatgggct cagtggcgat 7620agcactgacg gtccagtccc aggctttatt gaatgggatt gtggagcagc agaaggttct 7680gctgagcctg atagatcagc actccgagtt attaaaacta actatctggg gtgtaaaaaa 7740tcttcaggcc cgcctcacag ccttggagga atacgtagcg gaccaatcaa gactggcagt 7800atggggatgc tcattctctc aagtatgcca cactaatgta aagtggccta atgattcaat 7860agttcctaac tggacctcgg aaacatggct tgaatgggat aaaagagtga cagcaattac 7920aacaaatatg acaatagact tgcagagggc atatgaattg gaacaaaaga atatgtttga 7980gcttcaaaaa ttaggagatc tcacctcctg ggccagctgg ttcgacctca cgtggtggtt 8040taaatatatt aagataggaa ttcttataat aatagtgata ataggactta gaatattagc 8100ttgcttatgg tcagtattag gcaggtttag gcagggttac cgccctcttc cttatgtctt 8160caagggagac tatcaccgac cccacaacct caaacagcca gacaaagaaa gaggagaaga 8220gcaagacaga gaaaaacaga acatcagctc agagaattac aggccaggat ctggcagagc 8280ttggagcaaa gagcaagtag agacctggtg gaaggagtcc aggctctaca tttggttgaa 8340gagcacacaa gcagtaattg aatatgggtg gcaagagctc aaagcagcag gagcagaaat 8400atataaaata ttacagagcg ctgcgcagag gctatggagc ggagggcacc aactcggact 8460atcatgtatt agagcagcta cagcctttgg cagaggagtc agaaacattc ctagacgcat 8520cagacaagga gcagaagtct tactcaactg agttagactt aagacatcaa caagatgtaa 8580gcctccccac agaagaagaa cagccttggg aagaggaaga ggaggtaggc tttccagtct 8640acccacgaca gcctgtgcat gaagccacct ataaagactt gatagacctg tcccactttt 8700taaaagaaaa ggggggactg gaagggattt ggtggtctaa aagaagagaa gaaatcttgg 8760atatatatgc acaaaatgaa tggggaatta tacctgactg gcaggcttac acttcaggac 8820cggggatcag gtatccaaaa gcatttgggt tcctgtttaa actgatccca gtggcagttc 8880caccggaaca agagaacaat gaatgcaata ggctgctaaa ctcttctcag acaggaatcc 8940aggaagatcc atggggagaa aggctcatgt ggaagtttga ctctgctctt gcctatactt 9000tctatgctcc cataaagagg ccaggagact tcaagcatgt ccaaagtctt agctatgaag 9060cttataagaa ggaacctgac tgctgcaaga ggaagtggtg gcgcttctag ccgaccacag 9120agggttgcta tggcgatacc ctttaaaact gctaactctg gagggacttt ccactagtgc 9180atgcgcactg gactggggac tttccaggat gacgccgggt gggggagtgg tcagcccaat 9240ctggctgcat ataagcagct cgctttgcgc ttgtattgag tctctccctg agaggctacc 9300agattgagcc taggttgttc tctggtgagt ccttgaagga gtgcctgctt gtagccctgg 9360gcggttcgca ggcccctggc ttgtagctct gggtagctcg tcaggtgttc tggaaaggtc 9420ttgctaaggg gacgcctttg cttggtcttg gtagacctct agcagtctca gtggccagga 9480ggctgtggga ttgactaccg cttgcttgcc tttgatgctc aataaagctt acccgaatta 9540gaaaggcatt caagtgtact cgctcatttt gtctttggta gaaactctgg ttactggaga 9600tccctcagat ttgtgccaga cttctgatat ctagtgagag t 9641 23 518 PRT SIV - viral 23Ile Gly Ala Ser Ala Ser Gly Leu Arg Gly Arg Glu Leu Asp Glu Leu1 5 10 15Glu Lys Ile Arg Leu Arg Pro Ser Gly Lys Lys Lys Tyr Gln Leu Lys 20 25 30His Val Ile Trp Val Ser Lys Glu Leu Asp Arg Phe Gly Leu His Glu 35 40 45Lys Leu Leu Glu Thr Lys Glu Gly Cys Glu Lys Ile Leu Ser Val Leu 50 55 60Phe Pro Leu Val Pro Thr Gly Ser Glu Asn Leu Ile Ser Leu Tyr Asn65 70 75 80Thr Cys Cys Cys Ile Trp Cys Val His Ala Lys Val Lys Val Ala Asp 85 90 95Thr Glu Glu Ala Lys Glu Lys Val Lys Gln Cys Tyr His Leu Val Val 100 105 110Glu Lys Gln Asn Ala Ala Ser Glu Lys Glu Lys Gly Ala Thr Val Thr 115 120 125Pro Ser Gly His Ser Arg Asn Tyr Pro Ile Gln Ile Val Asn Gln Thr 130 135 140Pro Val His Gln Gly Ile Ser Pro Arg Thr Leu Asn Ala Trp Val Lys145 150 155 160Cys Ile Glu Glu Lys Lys Phe Ser Pro Glu Ile Val Pro Met Phe Ile 165 170 175Ala Leu Ser Glu Gly Cys Leu Pro Tyr Asp Leu Asn Gly Met Leu Asn 180 185 190Ala Ile Gly Asp His Gln Gly Ala Leu Gln Ile Val Lys Asp Val Ile 195 200 205Asn Asp Glu Ala Ala Asp Trp Asp Leu Arg His Pro Gln Met Gly Pro 210 215 220Met Pro Gln Gly Val Leu Arg Asn Pro Thr Gly Ser Asp Ile Ala Gly225 230 235 240Thr Thr Ser Ser Ile Glu Glu Gln Ile Glu Trp Thr Thr Arg Gln Gln 245 250 255Asp Gln Val Asn Val Gly Gly Ile Tyr Lys Gln Trp Ile Val Leu Gly 260 265 270Leu Gln Lys Cys Val Ser Met Tyr Asn Pro Val Asn Ile Leu Asp Ile 275 280 285Lys Gln Gly Pro Lys Glu Pro Phe Lys Asp Tyr Val Asp Arg Phe Tyr 290 295 300Lys Ala Leu Arg Ala Glu Arg Thr Asp Pro Gln Val Lys Asn Trp Met305 310 315 320Thr Gln Thr Leu Leu Ile Gln Asn Ala Asn Pro Asp Cys Lys Ala Ile 325 330 335Leu Lys Gly Leu Gly Met Asn Pro Thr Leu Glu Glu Met Leu Leu Ala 340 345 350Cys Gln Gly Val Gly Gly Pro Lys Tyr Lys Ala Gln Met Met Ala Glu 355 360 365Ala Met Gln Glu Val Gln Gly Lys Ile Met Met Gln Ala Ser Gly Gly 370 375 380Pro Pro Arg Gly Pro Pro Arg Gln Pro Pro Arg Asn Pro Arg Cys Pro385 390 395 400Asn Cys Gly Lys Phe Gly His Val Leu Arg Asp Cys Arg Ala Pro Arg 405 410 415Lys Arg Gly Cys Phe Lys Cys Gly Asp Pro Gly His Leu Met Arg Asn 420 425 430Cys Pro Lys Met Val Asn Phe Leu Gly Asn Ala Pro Trp Gly Ser Gly 435 440 445Lys Pro Arg Asn Phe Pro Ala Val Pro Leu Thr Pro Thr Ala Pro Pro 450 455 460Met Pro Gly Leu Glu Asp Pro Ala Glu Lys Met Leu Leu Asp Tyr Met465 470 475 480Lys Lys Gly Gln Gln Met Lys Ala Glu Arg Glu Ala Lys Arg Glu Lys 485 490 495Asp Lys Gly Pro Tyr Glu Ala Ala Tyr Asn Ser Leu Ser Ser Leu Phe 500 505 510Gly Thr Asp Gln Leu Gln 515 24 1016 PRT SIV - viral 24Phe Phe Arg Glu Cys Ser Leu Gly Gln Trp Gln Thr Gln Glu Leu Ser1 5 10 15Cys Arg Ala Thr Asp Pro Asn Gly Thr Pro Asp Ala Arg Ile Arg Gly 20 25 30Pro Ser Arg Glu Asp Ala Thr Gly Leu His Glu Glu Gly Ala Thr Asp 35 40 45Glu Gly Arg Glu Gly Ser Gln Thr Gly Glu Gly Gln Arg Pro Leu Arg 50 55 60Gly Gly Leu Gln Leu Pro Gln Phe Ser Leu Trp Asn Arg Pro Thr Thr65 70 75 80Val Val Glu Ile Glu Gly Gln Lys Val Glu Ala Leu Leu Asp Thr Gly 85 90 95Ala Asp Asp Thr Val Ile Lys Asp Leu Gln Leu Thr Gly Asn Trp Lys 100 105 110Pro Gln Ile Ile Gly Gly Ile Gly Gly Ala Ile Arg Val Lys Gln Tyr 115 120 125Phe Asn Cys Lys Ile Thr Val Ala Gly Lys Ser Thr His Ala Ser Val 130 135 140Leu Val Gly Pro Thr Pro Val Asn Ile Ile Gly Arg Asn Val Leu Lys145 150 155 160Lys Leu Gly Cys Thr Leu Asn Phe Pro Ile Ser Lys Ile Glu Thr Val 165 170 175Lys Val Thr Leu Lys Pro Gly Thr Asp Gly Pro Arg Ile Lys Gln Trp 180 185 190Pro Leu Ser Lys Glu Lys Ile Leu Ala Leu Gln Glu Ile Cys Asn Gln 195 200 205Met Glu Lys Glu Gly Lys Ile Ser Arg Ile Gly Pro Glu Asn Pro Tyr 210 215 220Asn Thr Pro Val Phe Cys Ile Lys Lys Lys Asp Gly Ala Ser Trp Arg225 230 235 240Lys Leu Val Asp Phe Arg Gln Leu Asn Lys Val Thr Gln Asp Phe Phe 245 250 255Glu Val Gln Leu Gly Ile Pro His Pro Gly Gly Leu Lys Gln Cys Glu 260 265 270Gln Ile Thr Val Leu Asp Ile Gly Asp Ala Tyr Phe Ser Cys Pro Leu 275 280 285Asp Glu Asp Phe Arg Lys Tyr Thr Ala Phe Thr Ile Pro Ser Val Asn 290 295 300Asn Gln Gly Pro Gly Ile Arg Tyr Gln Tyr Asn Val Leu Pro Gln Gly305 310 315 320Trp Lys Gly Ser Pro Ala Ile Phe Gln Ala Thr Ala Asp Lys Ile Leu 325 330 335Lys Thr Phe Lys Glu Glu Tyr Pro Glu Val Leu Ile Tyr Gln Tyr Met 340 345 350Asp Asp Leu Phe Val Gly Ser Asp Leu Asn Ala Thr Glu His Asn Lys 355 360 365Met Ile Asn Lys Leu Arg Glu His Leu Arg Phe Trp Gly Leu Glu Thr 370 375 380Pro Asp Lys Lys Phe Gln Lys Glu Pro Pro Phe Glu Trp Met Gly Tyr385 390 395 400Val Leu His Pro Lys Lys Trp Thr Val Gln Lys Ile Gln Leu Pro Glu 405 410 415Lys Glu Gln Trp Thr Val Asn Asp Ile Gln Lys Leu Val Gly Lys Leu 420 425 430Asn Trp Ala Ser Gln Ile Tyr Ser Gly Ile Lys Thr Lys Glu Leu Cys 435 440 445Lys Leu Ile Arg Gly Ala Lys Pro Leu Asp Glu Ile Val Glu Trp Thr 450 455 460Arg Glu Ala Glu Leu Glu Tyr Glu Glu Asn Lys Ile Ile Val Gln Glu465 470 475 480Glu Val His Gly Val Tyr Tyr Gln Pro Glu Lys Pro Leu Met Ala Lys 485 490 495Val Gln Lys Leu Thr Gln Gly Gln Trp Ser Tyr Gln Ile Glu Gln Glu 500 505 510Glu Asn Lys Pro Leu Lys Ala Gly Lys Tyr Ala Arg Thr Lys Asn Ala 515 520 525His Thr Asn Glu Leu Arg Thr Leu Ala Gly Leu Val Gln Lys Ile Ala 530 535 540Lys Glu Cys Ile Val Ile Trp Gly Arg Leu Pro Lys Phe Tyr Leu Pro545 550 555 560Leu Glu Arg Glu Val Trp Asp Gln Trp Trp His Asp Tyr Trp Gln Val 565 570 575Thr Trp Ile Pro Glu Trp Glu Phe Ile Ser Thr Pro Pro Leu Ile Arg 580 585 590Leu Trp Tyr Asn Leu Leu Lys Glu Pro Ile Pro Gly Glu Asp Val Tyr 595 600 605Tyr Val Asp Gly Ala Ala Asn Arg Asn Ser Lys Glu Gly Lys Ala Gly 610 615 620Tyr Tyr Thr Ala Arg Gly Lys Ser Lys Val Ile Ala Leu Glu Asn Thr625 630 635 640Thr Asn Gln Lys Ala Glu Leu Lys Ala Ile Glu Leu Ala Leu Lys Asp 645 650 655Ser Gly Pro Arg Val Asn Ile Val Thr Asp Ser Gln Tyr Ala Leu Gly 660 665 670Ile Leu Thr Ala Ser Pro Asp Gln Ser Asp Asn Pro Ile Val Arg Glu 675 680 685Ile Ile Asn Leu Met Ile Ala Lys Glu Ala Val Tyr Leu Ser Trp Val 690 695 700Pro Ala His Lys Gly Ile Gly Gly Asn Glu Gln Ile Asp Lys Leu Val705 710 715 720Ser Gln Gly Ile Arg Gln Val Leu Phe Leu Glu Gly Ile Asp Arg Ala 725 730 735Gln Glu Glu His Asp Lys Tyr His Asn Asn Trp Arg Ala Leu Ala Gln 740 745 750Glu Phe Ser Ile Pro Pro Ile Val Ala Lys Glu Ile Val Ala Gln Cys 755 760 765Pro Lys Cys Gln Ile Lys Gly Glu Pro Ile His Gly Gln Val Asp Ala 770 775 780Ser Pro Gly Thr Trp Gln Met Asp Cys Thr His Leu Glu Gly Lys Val785 790 795 800Ile Ile Val Ala Val His Val Ala Ser Gly Tyr Leu Glu Ala Glu Val 805 810 815Ile Pro Ala Glu Thr Gly Lys Glu Thr Ala His Phe Leu Leu Lys Leu 820 825 830Ala Gly Arg Trp Pro Val Lys His Leu His Thr Asp Asn Gly Pro Asn 835 840 845Phe Val Ser Glu Lys Val Ala Thr Val Cys Trp Trp Ala Gln Ile Glu 850 855 860His Thr Thr Gly Val Pro Tyr Asn Pro Gln Ser Gln Gly Val Val Glu865 870 875 880Ala Lys Asn His His Leu Lys Thr Ile Ile Glu Gln Val Arg Asp Gln 885 890 895Ala Glu Lys Leu Glu Thr Ala Val Gln Met Ala Val Leu Ile His Asn 900 905 910Phe Lys Arg Lys Gly Gly Ile Gly Glu Tyr Ser Pro Gly Glu Arg Ile 915 920 925Val Asp Ile Ile Thr Thr Asp Ile Leu Thr Thr Lys Leu Gln Gln Asn 930 935 940Ile Ser Lys Ile Gln Asn Phe Arg Val Tyr Tyr Arg Glu Gly Arg Asp945 950 955 960Gln Gln Trp Lys Gly Pro Ala Glu Leu Ile Trp Lys Gly Glu Gly Ala 965 970 975Val Val Ile Lys Glu Gly Thr Asp Leu Lys Val Val Pro Arg Arg Lys 980 985 990Ala Lys Ile Ile Arg Asp Tyr Gly Lys Ala Val Asp Ser Asn Ser His 995 1000 1005Met Glu Ser Arg Glu Glu Ser Ala 1010 1015 25 853 PRT SIV - viral 25Gln Trp Val Thr Val Tyr Tyr Gly Thr Pro Lys Trp His Pro Ala Arg1 5 10 15Thr His Leu Phe Cys Ala Thr Asp Asn Asn Ser Phe Trp Val Thr Thr 20 25 30Ser Cys Val Pro Ser Leu Leu His Tyr Glu Glu Gln His Ile Pro Asn 35 40 45Ile Thr Glu Asn Phe Thr Gly Pro Ile Thr Glu Asn Glu Val Ile Arg 50 55 60Gln Ala Trp Gly Ala Ile Ser Ser Met Ile Asp Ala Val Leu Lys Pro65 70 75 80Cys Val Lys Leu Thr Pro Tyr Cys Val Lys Met Lys Cys Thr Lys Gly 85 90 95Asp Thr Asp Thr Thr Glu Arg Thr Thr Ser Thr Thr Ser Ser Trp Ser 100 105 110Thr Ser Thr Pro Thr Ser Thr Pro Met Thr Pro Asn Thr Thr Gly Leu 115 120 125Asp Ile Asp Ser Asn Asn Thr Glu Pro Thr Thr Gln Glu Asn Arg Ile 130 135 140Cys Lys Phe Asn Thr Thr Gly Leu Cys Arg Asp Cys Arg Leu Glu Ile145 150 155 160Glu Glu Asn Phe Arg Tyr Gln Asp Ile Thr Cys Arg Asn Ser Ser Glu 165 170 175Asp Thr Glu Glu Cys Tyr Met Thr His Cys Asn Ser Ser Val Ile Thr 180 185 190Gln Asp Cys Asn Lys Ala Ser Thr Asp Lys Met Thr Phe Arg Leu Cys 195 200 205Ala Pro Pro Gly Tyr Val Leu Leu Arg Cys Arg Glu Lys Leu Asn Gln 210 215 220Thr Lys Leu Cys Gly Asn Ile Thr Ala Val Gln Cys Thr Asp Pro Met225 230 235 240Pro Ala Thr Ile Ser Thr Met Phe Gly Phe Asn Gly Thr Lys His Asp 245 250 255Tyr Asp Glu Leu Ile Leu Thr Asn Pro Gln Lys Ile Asn Glu Phe His 260 265 270Asp His Lys Tyr Val Tyr Arg Val Asp Lys Lys Trp Lys Leu Gln Val 275 280 285Val Cys Arg Arg Lys Gly Asn Arg Ser Ile Ile Ser Thr Pro Ser Ala 290 295 300Thr Gly Leu Leu Phe Tyr His Gly Leu Glu Pro Gly Lys Asn Leu Lys305 310 315 320Lys Gly Met Cys Gln Leu Lys Gly Leu Trp Gly Lys Ala Met His Gln 325 330 335Leu Ser Glu Glu Leu Arg Lys Ile Asn Gly Ser Ile Tyr Arg Lys Trp 340 345 350Asn Glu Thr Ala Gly Cys Arg Lys Leu Asn Lys Gln Asn Gly Thr Gly 355 360 365Cys Ser Leu Lys Thr Ile Glu Val Ser Glu Tyr Thr Thr Glu Gly Asp 370 375 380Pro Gly Ala Glu Thr Ile Met Leu Leu Cys Gly Gly Glu Tyr Phe Phe385 390 395 400Cys Asn Trp Thr Lys Ile Trp Lys Thr Trp Asn Asn Gln Thr Ser Asn 405 410 415Val Trp Tyr Pro Trp Met Ser Cys Asn Ile Arg Gln Ile Val Asp Asp 420 425 430Trp His Lys Val Gly Lys Lys Ile Tyr Met Pro Pro Ala Ser Gly Phe 435 440 445Asn Asn Glu Ile Arg Cys Thr Asn Asp Val Thr Glu Met Phe Phe Glu 450 455 460Val Gln Lys Lys Glu Glu Asn Lys Tyr Leu Ile Lys Phe Ile Pro Gln465 470 475 480Asp Glu Ile Gln Asn Gln Tyr Thr Ala Val Gly Ala His Tyr Lys Leu 485 490 495Val Lys Val Asp Pro Ile Gly Phe Ala Pro Thr Asp Val His Arg Tyr 500 505 510His Leu Pro Asp Val Lys Gln Lys Arg Gly Ala Val Leu Leu Gly Met 515 520 525Leu Gly Leu Leu Gly Leu Ala Gly Ser Ala Met Gly Ser Val Ala Ile 530 535 540Ala Leu Thr Val Gln Ser Gln Ala Leu Leu Asn Gly Ile Val Glu Gln545 550 555 560Gln Lys Val Leu Leu Ser Leu Ile Asp Gln His Ser Glu Leu Leu Lys 565 570 575Leu Thr Ile Trp Gly Val Lys Asn Leu Gln Ala Arg Leu Thr Ala Leu 580 585 590Glu Glu Tyr Val Ala Asp Gln Ser Arg Leu Ala Val Trp Gly Cys Ser 595 600 605Phe Ser Gln Val Cys His Thr Asn Val Lys Trp Pro Asn Asp Ser Ile 610 615 620Val Pro Asn Trp Thr Ser Glu Thr Trp Leu Glu Trp Asp Lys Arg Val625 630 635 640Thr Ala Ile Thr Thr Asn Met Thr Ile Asp Leu Gln Arg Ala Tyr Glu 645 650 655Leu Glu Gln Lys Asn Met Phe Glu Leu Gln Lys Leu Gly Asp Leu Thr 660 665 670Ser Trp Ala Ser Trp Phe Asp Leu Thr Trp Trp Phe Lys Tyr Ile Lys 675 680 685Ile Gly Ile Leu Ile Ile Ile Val Ile Ile Gly Leu Arg Ile Leu Ala 690 695 700Cys Leu Trp Ser Val Leu Gly Arg Phe Arg Gln Gly Tyr Arg Pro Leu705 710 715 720Pro Tyr Val Phe Lys Gly Asp Tyr His Arg Pro His Asn Leu Lys Gln 725 730 735Pro Asp Lys Glu Arg Gly Glu Glu Gln Asp Arg Glu Lys Gln Asn Ile 740 745 750Ser Ser Glu Asn Tyr Arg Pro Gly Ser Gly Arg Ala Trp Ser Lys Glu 755 760 765Gln Val Glu Thr Trp Trp Lys Glu Ser Arg Leu Tyr Ile Trp Leu Lys 770 775 780Ser Thr Gln Ala Val Ile Glu Tyr Gly Trp Gln Glu Leu Lys Ala Ala785 790 795 800Gly Ala Glu Ile Tyr Lys Ile Leu Gln Ser Ala Ala Gln Arg Leu Trp 805 810 815Ser Gly Gly His Gln Leu Gly Leu Ser Cys Ile Arg Ala Ala Thr Ala 820 825 830Phe Gly Arg Gly Val Arg Asn Ile Pro Arg Arg Ile Arg Gln Gly Ala 835 840 845Glu Val Leu Leu Asn 850 26 32 PRT SIM27.ENV 26Arg Leu Thr Ala Leu Glu Glu Tyr Val Ala Asp Gln Ser Arg Leu Ala1 5 10 15Val Trp Gly Cys Ser Phe Ser Gln Val Cys His Thr Asn Val Lys Trp 20 25 30 27 32 PRT SIV-Mandrill, MNDGB1 27Arg Leu Thr Ser Leu Glu Asn Tyr Ile Lys Asp Gln Ala Leu Leu Ser1 5 10 15Gln Trp Gly Cys Ser Trp Ala Gln Val Cys His Thr Ser Val Glu Trp 20 25 30 28 32 PRT HIV1-N, YBF30 28Lys Val Leu Ala Ile Glu Arg Tyr Leu Arg Asp Gln Gln Ile Leu Ser1 5 10 15Leu Trp Gly Cys Ser Gly Lys Thr Ile Cys Tyr Thr Thr Val Pro Trp 20 25 30 29 32 PRT HIV1-C, 96bw05.02 29Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly1 5 10 15Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp 20 25 30 30 32 PRT HIV1-O, ANT70C 30Arg Leu Leu Ala Leu Glu Thr Leu Leu Gln Asn Gln Gln Leu Leu Ser1 5 10 15Leu Trp Gly Cys Lys Gly Lys Leu Val Cys Tyr Thr Ser Val Lys Trp 20 25 30 31 32 PRT SIV-CPZ, CPZGAB 31Arg Leu Leu Ala Val Glu Arg Tyr Leu Gln Asp Gln Gln Ile Leu Gly1 5 10 15Leu Trp Gly Cys Ser Gly Lys Ala Val Cys Tyr Thr Thr Val Pro Trp 20 25 30 32 32 PRT HIV1-O, MVP5180 32Arg Leu Gln Ala Leu Glu Thr Leu Ile Gln Asn Gln Gln Arg Leu Asn1 5 10 15Leu Trp Gly Cys Lys Gly Lys Leu Ile Cys Tyr Thr Ser Val Lys Trp 20 25 30 33 32 PRT SIV-1hoesti 33Arg Leu Thr Ala Leu Glu Glu Tyr Val Lys His Gln Ala Leu Leu Ala1 5 10 15Ser Trp Gly Cys Gln Trp Lys Gln Val Cys His Thr Asn Val Glu Trp 20 25 30 34 32 PRT SIV-SYKES 34Arg Leu Thr Ala Leu Glu Thr Tyr Leu Arg Asp Gln Ala Ile Leu Ser1 5 10 15Asn Trp Gly Cys Ala Phe Lys Gln Ile Cys His Thr Ala Val Thr Trp 20 25 30 35 32 PRT SIV-CPZ, CPZANT 35Arg Met Leu Ala Val Glu Lys Tyr Leu Arg Asp Gln Gln Leu Leu Ser1 5 10 15Leu Trp Gly Cys Ala Asp Lys Val Thr Cys His Thr Thr Val Pro Trp 20 25 30 36 32 PRT SIV-CPZ-US 36Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Ile Leu Gly1 5 10 15Leu Trp Gly Cys Ser Gly Lys Thr Ile Cys Tyr Thr Thr Val Pro Trp 20 25 30 37 32 PRT HIV1-F, 93br020.1 37Arg Val Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly1 5 10 15Leu Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp 20 25 30 38 32 PRT HIV1-A, 92ug037 38Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly1 5 10 15Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Pro Thr Asn Val Pro Trp 20 25 30 39 32 PRT HIV1-H, 90cr056 39Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly1 5 10 15Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Asn Val Pro Trp 20 25 30 40 32 PRT HIV1-D, NDK 40Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp Gln Gln Leu Leu Gly1 5 10 15Ile Trp Gly Cys Ser Gly Arg His Ile Cys Thr Thr Asn Val Pro Trp 20 25 30 41 32 PRT HIV2-B, UC1 41Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Leu Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 42 32 PRT SIV-D, MNE 42Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ala Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 43 32 PRT SIV-D, MM239 43Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ala Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 44 32 PRT SIV, SME543 44Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 45 32 PRT SIV-D, SMM-PBJ-6P9 45Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 46 32 PRT SIV-D, STM 46Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 47 32 PRT HIV2-A, CAM2 47Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 48 32 PRT HIV2-A, GH1 48Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 49 32 PRT HIV2-B, EHO 49Arg Val Thr Ala Ile Glu Lys Tyr Leu Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 50 32 PRT SIV-SMM, PGM 50Arg Val Thr Ala Ile Glu Lys Tyr Arg Lys Asp Gln Ala Gln Leu Asn1 5 10 15Ser Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 51 32 PRT SIV-VERVET, AGM155 51Arg Val Thr Ala Leu Glu Lys Tyr Leu Ala Asp Gln Ala Arg Leu Asn1 5 10 15Ala Trp Gly Cys Ala Trp Lys Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 52 32 PRT SIV-VERVET, AGM3 52Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn1 5 10 15Ala Trp Gly Cys Ala Trp Lys Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 53 32 PRT SIV-VERVET, AGMSAB1 53Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn1 5 10 15Ile Trp Gly Cys Ala Phe Arg Gln Val Cys His Thr Thr Val Leu Trp 20 25 30 54 32 PRT SIV-VERVET, AGMTY6 54Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn1 5 10 15Ser Trp Gly Cys Ala Trp Lys Gln Val Cys His Thr Thr Val Glu Trp 20 25 30 55 32 PRT SIV-GRIVET, AGM677A 55Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn1 5 10 15Ser Trp Gly Cys Ala Trp Lys Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 56 32 PRT SIV-VERVET, REV 56Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn1 5 10 15Val Trp Gly Cys Ala Trp Lys Gln Val Cys His Thr Thr Val Pro Trp 20 25 30 57 32 PRT SIV-TANTALUS, TAN1 57Arg Val Thr Ala Leu Glu Lys Tyr Leu Glu Asp Gln Thr Arg Leu Asn1 5 10 15Leu Trp Gly Cys Ala Phe Lys Gln Val Cys His Thr Thr Val Pro Trp 20 25 30

Claims

1. An isolated and purified nucleic acid molecule comprising SEQ ID NO: 21.

2. An isolated immunodeficiency virus comprising SEQ ID NO: 21.

3. The virus of claim 2, further comprising a nucleic acid molecule selected from the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO; 20 and SEQ ID NO: 22.

4. An isolated immunodeficiency virus comprising SEQ ID NO: 21 or a variant thereof, wherein said variant encodes SEQ ID NO: 26, wherein the arginine or lysine in position 3 is substituted with a different amino acid.

5. An isolated immunodeficiency virus of claim 4, wherein said different amino acid is a polar amino acid or an amino acid having an aliphatic side chain.

6. The isolated immunodeficiency virus of claim 5, wherein said polar amino acid is serine and said amino acid having an aliphatic side chain is alanine.