HIV-1 virus isolates of a subtype and its differential diagnostics, a vaccine against HIV-1 virus infections of this subtype and method of producing same, use of the HIV-1 virus isolates

Abstract

Three new HIV-1 isolates HIV-1 D747(ECACC V92082718), HIV-1 D757(ECACC V92082719) and HIV-1 D760(ECACC V92082720) are disclosed, which represent a further independent subtype of the HIV-1 family and have been recovered from Indian patients which at the time when the virus was isolated showed no typical AIDS symptoms. Also disclosed are vaccines against HIV-1 infections by this subtype and a process for producing the same, as well as the use of the HIV-1 infection, as well as for differential diagnosis.

Description

The invention relates to new HIV-1 virus isolates of a subtype, vaccines against HIV-1 virus infections of this subtype, methods of producing same, and the use of the virus isolates for the production of vaccines and for differential diagnostics.

Hitherto, efforts to develop agents for the prophylaxis and stherapy of HIV infections have focused on the inhibition of the reverse transcriptase or some other enzyme of the HIV-1 virus such as, for example, protease. Thereby a specific inhibition of viral replication in contrast to cellular replication is intended to be accomplished. Nevertheless, the antiviral agents of prior art suffer from the drawback that they are accompanied by a relatively high toxicity towards the cells, i.e. they do not only affect the virus.

Those groups of substances which have been identified as being active against HIV viruses include, inter alia, various nucleoside analogues (azidothymidine, di-deoxyinosine and di-deoxycytidine). However, a massive formation of resistence of the virus has been detected after some relatively short periods of therapy with these substances {Zimmermann et al., Abstract No. 3656, IV International Conference on AIDS, Stockholm, 1988, Rübsamen-Waigmann et al., Infection 19, Suppl. 2, 77-82, 1991}. Furthermore, all of the substances mentioned produce considerable side-effects, at least when applied in higher doses.

Another inhibitor of reverse transcriptase is the substance Suramin. However, this substance, due to its toxicity towards the mammal organism, is also not suitable for prophylaxis or therapy of HIV-virus infections {H. Mitsuya et al. “Suramin Protection of T-Cells in vitro against Infectivity and Cyto-pathic Effect of HTLV-III, Science 226 (1984), pages 172-174}.

Further development has led to reverse transcriptase inhibitors which are less toxic towards the mammal organism. These include substances such as dextran sulfate and pentosan polysulfate, which have proven to display a HIV-1-inhibiting effect in vivo, as has been described in DE 36 01 136 and in EP 0 293 826.

In addition to a chemotherapeutic treatment of HIV infections there is basically the possibility of a gene therapy or immunotherapy. Gene therapy comprises the incorporation of parts of viral nucleic acids in human cells, especially in the target cells of the HIV virus, for example the CD4-positive cells of the immune system. Then, the viral messenger RNA (m-RNA) can be neutralized by the formation of an “antisense” RNA, i.e. an RNA complementary to m-RNA, and hence the virus proliferation can be terminated. In some other form, oligonucleotides or structures chemical related thereto that are complementary to m-RNA can be employed. In immunotherapy, antigens are administered after the infection which are expected to support the immune response to HIV.

Meanwhile, the World Health Organization (WHO) estimates a number of at least 13 million of HIV-infected people worldwide; no country has been left free from infections with HIV-1 or HIV-2 or both viruses at the same time. It is urgently necessary to develop a vaccine for protection from HIV infections in order to prevent the epidemic from farther spreading. Here, and also in immunotherapy, the main problem is the high variability of the HIV viruses: a prophylactic inoculation should and must include all of the possible virus variants. Epidemiologic investigations in combination with the genetic characterization of the viruses produced the result that several subtypes do already exist in both virus families {Myers et al., Human Retroviruses and AIDS, Los Alamos, 1991; Dietrich et al., Nature 342, 948-950, 1989}, which subtypes are significantly distinguished from one another with respect to their hereditary information to a degree such that one single vaccine will not be capable to be active against all variants. Moreover, these subtypes are also subject to different geographic distributions.

The present invention provides three new HIV 1 virus isolates HIV-1 D757 , HIV-1 D747 , HIV-1 D760 , which, surprisingly, form a further independent subtype of the HIV-1 family and have been recovered from three Indian patients who, at the time of virus isolation, did not show any typical AIDS symptoms. Furthermore, the invention also includes virus isolates of the HIV-1 type which are up to 30%, and preferably up to 5%, divergent from HIV-1 D757 , HIV-1 D747 , and HIV-1 D760 .

The virus isolates, in accordance with the regulations according to the Budapest Treaty, have been deposited with the European Collection of Animal Cell Cultures (ECACC), Porton Down, Salisbury, Wiltshire, United Kingdom, on Aug. 27, 1992, under the following Accession Numbers:

HIV-1 D747 —ECACC V92082718

HIV-1 D757 —ECACC V92082719

HIV-1 D760 —ECACC V92082720

The virus isolates proliferate on fresh mononuclear cells of peripheral blood, i.e. lymphocytes and macrophages.

The invention further provides a vaccine having an activity spectrum against this specific HIV-1 subtype.

The vaccine contains, as the active ingredient, the peptides

1. MPNGTKSNS SEQ ID NO:7, MPNGTKGNS SEQ ID NO:8, MPNGTKSNL SEQ ID NO:9,

2. RNEKDLLALDSWKN SEQ ID NO:10,

combinations comprising said peptides or longer or shorter subpeptides thereof being up to 7 amino acids in length.

Said peptides are derived from the env region of the strains according to the invention (cf. FIG. 1 ). The nucleotide sequences of these viruses in the env gene over a range of 1.8 kb are only to 79.4-81.6% homologous with viruses of the North American/European subtype and to 78.9-81.2% homologous with prototype viruses of the Central African subtype. The homology on the amino acid level is 72.1-75.9% and 71.2-74.2%, respectively (cf. Table). Thus, these viruses genetically are to be classified between these two subtypes and form some further independent subtype which is also distinguished from the subtypes found in Rwanda/Uganda and in Northern Thailand by genetic equidistance.

Upon comparison of the amino acid sequences of the env proteins of HIV-1 D757 , HIV-1 D747 , HIV-1 D760 with the consensus sequences as derived for all of the HIV env sequences already published, there result for the env region two short ranges, in which the three Indian sequences are different from all of the other HIV-1 sequences in 7 of 9 and in 7 of 14 amino acids, respectively (FIG. 1 ). Peptides from these regions are preferably suitable for a vaccine having a specific spectrum of activity against the Indian subtype, and particularly so, if the vaccine consists of a combination of these peptides.

The peptides according to the invention are synthetically produced and, if advantageous, are chemically modified. These peptides or longer as well as shorter subpeptides, down to 7 amino acids in length, thereof are also a constituent of this invention, and so are their modified forms.

Furthermore, the invention also relates to a vaccine which contains, as the active ingredient, peptides from variable regions of other genes of HIV-1 D757 , HIV-1 D747 , HIV-1 D760 , if the deviation from the corresponding sequence of HIV-1 viruses of other subtypes is more than 30%.

In the vaccine, there may further be used antigens from the viruses according to the invention or peptide combinations or combinations of peptides and antigens. More specifically, the use of such antigens or peptides is preferred which, within the loop of the coat glycoprotein (amino acids 423-450, relative to HIV-1 Lai ), is responsible for binding to the CD4-receptor, contain a glycosylation site (NXT/S) immediately in front of cysteine 450 (HIV-1 Lai ). This glycosylation site is typical for the Indian viruses HIV-1 D757 , HIV-1 D747 and HIV-1 D760 . The amino acid regions of the HIV-1 D757 , HIV-1 D747 and HIV-1 D760 that correspond to the amino acids 423-450 of HIV-1 Lai are amino acids 294-321 of SEQ ID NO:2, amino acids 296-323 of SEQ ID NO:4, or amino acids 304-331 of SEQ ID NO:6 respectively. This glycosylation site has not been encountered among 29 HIV-1 env-genes that have been sequenced worldwide.

One preferred embodiment is a vaccine which is employed for prophylaxis prior to infections. Another preferred embodiment consists of that the vaccine is used as an immunotherapeutic to be employed after the infection and also covers the spectrum of variants of this subtype. The vaccine is administered either for injection with adjuvant or as an oral, genital or rectal form of application, e.g. via nanoparticles.

Furtheron, the subject matter of the invention comprises a process for producing a vaccine against HIV-1 virus infections from the viruses HIV-1 D757 , HIV-1 D747 and HIV-1 D760 as well as the use of these viruses for the production of a vaccine.

In still one further embodiment, the viruses HIV-1 D757 1 HIV-1 D747 and HIV-1 D760 are transferred into a suitable host animal and allowed to proliferate therein. Then, the antibodies formed, after appropriate work-up as also known in the art for other vaccines, are used as a passive vaccine against HIV virus infections. As the host animals, more particularly, there may be used, suitable types of monkeys, but also animals that can be immunized without developing HIV symptoms (e.g. rabbits) {Filice et al., Nature 335 (1988), 366-368}.

Human monoclonal antibodies against HIV-1 D757 , HIV-1 D747 and HIV-1 D760 are also suitable for producing a vaccine for a protection against HIV-1 virus infections of this subtype.

In a further embodiment, in a suitable vector, DNA from which a RNA complementary to the viral m-RNA can be fully or partially transcribed, is transfected into human cells of the immune system and, hence, is conveyed into man. Thus, the viral m-RNA is competitively excluded from the further augmentation cycle. Likewise, synthetic oligonucleotides can be used for neutralizing the viral m-RNA.

In addition to the applications for therapy and vaccine production, HIV-1 D757 , HIV- 1 D747 and HIV- 1 D760 can also be used for differential diagnostics in order to distinguish infections with this subtype from other subtypes. For differential diagnostics, selected regions of the DNA of HIV-1 D757 , HIV-1 D747 and HIV-1 D760 are utilized which either do not occur at all in the prototype HIV-1 Lai or are significantly different therefrom (by more than 30%). From these regions, peptides or nucleic acids for diagnostics are prepared according to conventional methods (labelling with radioactive isotopes, immunofluorescence test, ELISA etc.).

Therefore, it is also a constituent of this invention to use HIV-1 D757 , HIV-1 D747 and HIV-1 D760 , or antigens, peptides or nucleic acids thereof, for the differential diagnostics for differentiating between infections with the subtype, characterized by HIV- 1 D757 , HIV-1 D747 or HIV-1 D760 , and infections with other HIV-1 subtypes as defined by the prototypes HIV-1 Lai (U.S.A./Europe) HIV-1 Mal (Central Africa), HIV-1 u455 (Uganda/Rwanda) and Northern Thailand.

It is also possible to employ peptide residues or PCR tests based on HIV-1 D757 , HIV-1 D747 or HIV-1 D760 , by means of which distinction can be made between viruses of this subtypes from other HIV-viruses.

Hereinbelow, the Figures and the Table are described:

The Table shows the nucleotide and amino acid sequence homology between HIV-1 D757 , HIV-1 D747 or HIV-1 D760 and other HIV-1 virus subtypes in percent. The sequences were compared by using Mikrogenie™ sequencing software by the company Beckman.

Table 2 shows the amino acid sequences in single character notation of the three Indian env clones in comparison to the corresponding sections of other subtypes. Highlighted are the two peptides 1 and 2, in which the Indian subtype is mainly different from the other sequences, and the additional glycolisation site (underlined) in immediate vicinity to the CD4 binding domain.

(−) denotes identical amino acids;

(.) denotes missing aminoacids.

Table 3 shows the relation of the sequences HIV-1 D757 , HIV-1 D747 or HIV-1 D760 to the remaining viruses in the phylogenetic tree of the viruses. This tree was established with the use of PAUP {Smith, T. F. et al., Nature 333, 573-575 (1988)} and the Version 3.21 of the PHYLIP bootstrappin algorithm.

TABLE 1
Homology of Indian HIV-1 isolates and American/European or prototypical African HIV-1
sequences (1.8 kb PCR-fragment, corresponding to positions 6129-7976 of HIV-1 Lai )
HIV-1	Lai	SF2	Eli	Mal	SIVepz
D757	79.7 (75.7)	81.6 (75.9)	81.2 (74.2)	80.6 (73.7)	66.1 (61.2)
D747	79.4 (73.5)	80.9 (75.6)	80.7 (72.8)	78.9 (73.2)	65.8 (63.2)
D760	80.7 (72.1)	81.4 (73.6)	80.9 (71.2)	80.2 (71.7)	66.1 (61.0)
Lai		90.0 (84.1)	83.7 (76.2)	82.8 (74.3)	65.0 (60.1)
SF2			83.8 (75.6)	82.8 (74.6)	64.3 (62.0)
Eli				85.2 (76.9)	65.7 (61.9)
Mal					66.4 (63.2)

TABLE 2
HIV-1                                                                        Bru ------------------S-K--DLGNATN-NSSN.TNSSSGEMMMEKG--------IS-
HIV-1                                                                        SF2 -----------------------DLGKATN-NSSN.WKEEI......KG--------I--
HIV-1                                                                        D757 SLWDQSLKPCVKLTPLCVTLNCTNA...NVTYDN..........GNYTEEIKNCSFNTTT
HIV-1                                                                        D747 --------------------H----TYS-S--NS..........T.-N------------
HIV-1                                                                        D760 --------------------E-G-VNAT-I-NNGE...NNPTNIT--R------P--A--
HIV-1                                                                        Eli ----------------------SD-...ELRNNGTMGNNVTTEEK....GM------V--
HIV-1                                                                        Mal ------------------------VNGTA-NGT-AGSNRTNAELKMEIG-V------I-P
SIVcpz                           --------------------Q-SK-NFSQA.......KNLTNQTSSPPL-M------V--
HIV-1                                                                        Bru SI-GKV--EY-F-----II-I-NDTT-.....-T-TS----V----------E-------
HIV-1                                                                        SF2 SI--KI--EN---RN-----I-NASTTTNYTN----H--R-V----------E-------
HIV-1                                                                        D757 ELRDQKQKVAALFYKLDVVPLDGNDNSS....YRLINCNTSAITQACPKVSFDPIPIHYC
HIV-1                                                                        D747 ----K----Q-----------NTT----....----------------------------
HIV-1                                                                        D760 -I--RQ---Y----R--I----N-N--T....------------------T---------
HIV-1                                                                        Eli V-K-K--Q-Y----R--I--I-NDSSTNS.TN--------------------E-------
HIV-1                                                                        Mal VGS-KR-E.Y-T--N--L-QI-D...-DN.SS---------V--------T---------
SIVcpz                           ----K-KQ-YS---VE---N-GNEN-T.....--I-----T--------T--E-------
HIV-1                                                                        Bru ----F----------------T----VQ-----R---------------E-VV---A-FT
HIV-1                                                                        SF2 T---F------------K---T----VQ-----R-I-------------E-VV---D-FT
HIV-1                                                                        D757 APAGYAILKCNNKTFNGTGPCHNVSTRTCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLA
HIV-1                                                                        D747 -G---------------------I--VQ-------------------------------T
HIV-1                                                                        D760 --------------------------VQ-----S-------------------------T
HIV-1                                                                        Eli ----F-----RD-K-------T----VQ-----R---------------E-V-------T
HIV-1                                                                        Mal ----F------D-K----EI-K----VQ---------------------E--M------T
SIVcpz                           ----F------D-D-S-K-K-T----VH---------T----I-------N-TV-V--KS
HIV-1                                                                        Bru D-A-----Q-----E-N--------------QR---RA-VTI-K-.-NM--------RA-
HIV-1                                                                        SF2 --A-----Q--E--A-N------------Y-..---RA-HT--R------K------RAQ
HIV-1                                                                        D757 NNVKTIIVHLNQSVRIVCTRPNNNTRKSIRI..GPGQTFYATGDIIGDIRQAHCNISEGK
HIV-1                                                                        D747 --------------E--Y---------GV--..---Q--------------------KH-
HIV-1                                                                        D760 D-------------EV---------------..---Q---------------------D-
HIV-1                                                                        Eli --A-N--A---E--K-T-A--YQ---QRTP-..-L--SL-T-R.SRSI-G-------RAQ
HIV-1                                                                        Mal D-T-N---Q--ET-T-N----G----RG-HF..----AL-T--.-V----R-Y-T-N-TE
SIVcpz                           K-TDVW--Q-VEA-SLN-H--G----GEVQ-..---M---NIENVV--T-S-Y-K-NGTT
HIV-1                                                                        Bru --A--KQIAS--R-Q-G-N--.-I-KQ----DP--V------G-------STQ-----WF
HIV-1                                                                        SF2 --N--EQIV---R-Q-G-N--.-V-NQ----DP--VM--------------TQLF.....
HIV-1                                                                        D757 WNETLQRVGKKLAEYFPN.KT.IKFASSSGGGLEITTHSFNCRGEFFYCNTSNLFNSTY.
HIV-1                                                                        D747 --------------H---.--.-R-------D--------------------D---G--.
HIV-1                                                                        D760 --------------H---.--.----A----D-----Y--------------G---G--.
HIV-1                                                                        Eli -SK---Q-AR--GTLL.-KTI.---KP----DP---------G---------G-----WN
HIV-1                                                                        Mal -DK---Q-AV--GSLL.-KTK.-I-N-----DP-------------------K-----WQ
SIVcpz                           --R-VEE-K-A--TSSNRTAAN-TLNRA---DP-V-H-M---G---------QI-.....
HIV-1                                                                        Bru NSTWSTEGSNNTEGSD---LP-----F--------K-------S-Q-R-S--------T-
HIV-1                                                                        SF2 NNTWRLNHTEGTKG-D--ILP--------------K-------G-Q-S-S--------T-
HIV-1                                                                        D757 .....MPNGTKGNSNSTITIQCRIKQIINMWQEVGRAMYAPPIEGNITCESNITGLLLVR
HIV-1                                                                        D747 .....------S--S-----P----------------------A-----K-----I----
HIV-1                                                                        D760 .....------S-L------P------V-L------------FAR----K----------
HIV-1                                                                        Eli ISAWNNITESNNST-TN--L--------K-.VAGRK-I------R--L-S--------T-
HIV-1                                                                        Mal NNG.ARLSNSTESTG-.--LP-----------KT-K-------A-V-N-L------I-T-
SIVcpz                           .........-DNIT-GI-ILP---R--VSS-MR---GI-----R-----N--------TS
HIV-1                                                                        Bru ---NN.--G.S-I---------D------------K-E-------K------....Q---
HIV-1                                                                        SF2 ----NVT-D.T-V---------D-----------IK-E---I---K------....Q---
HIV-1                                                                        D757 DGGTESNNT..ETFRPGGG-MRNNWRSELYKYKVVEIKPLGVAPTTAKRRVV....EREK
HIV-1                                                                        D747 ---IEL-D-KT--------E--D-----------------------------....----
HIV-1                                                                        D760 ---EDT-D..T-I-S-------D-----------------------------....----
HIV-1                                                                        Eli ---..I--STN-----------D------------Q-E-------R------....----
HIV-1                                                                        Mal ---NS-D-SDN--L--------D--I---------R-E-------K------....----
SIVcpz                           -TPVTN-SGNL.----T--N-KDI-----------R-E--S----K-R-HT-ARQKD-Q-
HIV-1                                                                        Bru -----.---L--------------R-------------------N---------------
HIV-1                                                                        SF2 -----V--M--------------V-L------------------N---------------
HIV-1                                                                        D757 RAVGI.GAVFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQSNLLRAIEAQQHLLQLT
HIV-1                                                                        D747 -----.---------------------V--------------------------------
HIV-1                                                                        D760 ----L.-------------------I----------------------------------
HIV-1                                                                        Eli --I-L.--M--------------R-V---------M-------N----------------
HIV-1                                                                        Mal --I-L.--M----------------L-----------------N----------------
SIVcpz                           --AFGL--L---------------AV-----------------N---K-----------S
HIV-1                                                                        Bru --------A-I--V--------------C--------A----A---.-K-LEQ-------
HIV-1                                                                        SF2 --------A----V----R---------C--------A----A---.-K-LED-------
HIV-1                                                                        D757 VWGIKQLQTRVLAIERYLKDQQLLGIWGRSGKLICTTNVPWNSSWS.NRSQTDIWDNMTW
HIV-1                                                                        D747 I-------A----------E--------C--------T--------.-------------
HIV-1                                                                        D760 -------------------------M--C--------A--------.-------------
HIV-1                                                                        Eli --------A-I--V--------------C---H-------------.---LNE--Q----
HIV-1                                                                        Mal --------A----V----Q--R---M--C---H----F--------.---LD---N----
SIVcpz                           I--V----A-L--V----Q---I--L--C---AV-Y-T-------PGSN-TD---G-L--
HIV-1                                                                        Bru -E---........................................--N---SL-HS-I-E
HIV-1                                                                        SF2 ---E-........................................--D---N---T---E
HIV-1                                                                        D757 MQWDR........................................EISNYTDTIYRLLED
HIV-1                                                                        D747 -----........................................------E--------
HIV-1                                                                        D760 -----........................................------N--------
HIV-1                                                                        Eli -E-E-........................................--D---GL--S-I-E
HIV-1                                                                        Mal ---EK........................................------GI--N-I-E
SIVcpz                           Q---KLVSNYTGKIFGLLEEAQSQQEKNERDLLELDQWASLWNWFD-T---GK-FG---E
HIV-1                                                                        Bru ------K--QE--E--K-AS-----N------------------V--R-V----------
HIV-1                                                                        SF2 ------K--QE--E--K-AS------------------------V--R-V----------
HIV-1                                                                        D757 SQNQQERNEKDLLALDSWKNLWNWFSITNWLWYIKIFIMIVGGLIGLKIIFAVLSIVNRV
HIV-1                                                                        D747 --------------------------------------I--------R------C-----
HIV-1                                                                        D760 -----------------------------------------------R------------
HIV-1                                                                        Eli --T---K---E--E--K-AS--------Q-----------I------R-V-----L----
HIV-1                                                                        Mal --I---K---E--E--K-AS-------SK-----R---IV-------R-------L----
SIVcpz                           A-S---K--R---E--Q-AS-----D--K--------L-A---I---R--MT-F-V-R--
HIV-1                                                                        Bru ----------- SEQ ID NO: 11
HIV-1                                                                        SF2 ----------- SEQ ID NO: 12
HIV-1                                                                        D757 RQGYSPLSFQT SEQ ID NO: 2
HIV-1                                                                        D747 KA--------- SEQ ID NO: 4
HIV-1                                                                        D760 ----------- SEQ ID NO: 6
HIV-1                                                                        Eli ----------- SEQ ID NO: 13
HIV-1                                                                        Mal --------L-- SEQ ID NO: 14
SIVcpz                           --------L-- SEQ ID NO: 15

TABLE 3

15 1 1932 DNA Human immunodeficiency virus HIV-1(D757) 1c agt tta tgg gat caa agc cta aag cca tgt gta aag ttg acc cca ctc 49 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15tgt gtc act tta aat tgt aca aat gca aat gtt acc tat gat aat ggt 97Cys Val Thr Leu Asn Cys Thr Asn Ala Asn Val Thr Tyr Asp Asn Gly 20 25 30aac tac act gaa gaa ata aaa aat tgc tct ttc aat aca act aca gaa 145Asn Tyr Thr Glu Glu Ile Lys Asn Cys Ser Phe Asn Thr Thr Thr Glu 35 40 45cta aga gat cag aaa cag aaa gtt gct gca ctt ttt tat aaa ctt gat 193Leu Arg Asp Gln Lys Gln Lys Val Ala Ala Leu Phe Tyr Lys Leu Asp 50 55 60gta gta cca ctt gat ggt aat gat aac tct agt tat aga tta ata aat 241Val Val Pro Leu Asp Gly Asn Asp Asn Ser Ser Tyr Arg Leu Ile Asn 65 70 75 80tgt aat acc tca gcc ata aca caa gcc tgt cca aag gtc tct ttt gac 289Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Asp 85 90 95cca atc cct ata cat tat tgt gct cca gct ggt tat gcg att cta aag 337Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Tyr Ala Ile Leu Lys 100 105 110tgt aat aat aag aca ttc aat ggg aca gga cca tgc cat aat gtc agc 385Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys His Asn Val Ser 115 120 125aca cgt aca tgt aca cat gga att aag cca gta gta tca act caa cta 433Thr Arg Thr Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu 130 135 140ctg tta aat ggt agc cta gca gaa gga gag ata ata att aga tct gaa 481Leu Leu Asn Gly Ser Leu Ala Glu Gly Glu Ile Ile Ile Arg Ser Glu145 150 155 160aat ctg gca aac aat gtc aaa aca ata ata gta cat ctt aat caa tct 529Asn Leu Ala Asn Asn Val Lys Thr Ile Ile Val His Leu Asn Gln Ser 165 170 175gta aga att gtg tgt aca aga ccc aac aat aat aca aga aaa agt ata 577Val Arg Ile Val Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile 180 185 190agg ata gga cca gga caa aca ttc tat gca aca gga gac ata ata gga 625Arg Ile Gly Pro Gly Gln Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly 195 200 205gac ata aga caa gca cat tgt aac att agt gaa ggt aaa tgg aat gaa 673Asp Ile Arg Gln Ala His Cys Asn Ile Ser Glu Gly Lys Trp Asn Glu 210 215 220act tta caa agg gta ggt aaa aaa tta gca gaa tac ttc cct aat aaa 721Thr Leu Gln Arg Val Gly Lys Lys Leu Ala Glu Tyr Phe Pro Asn Lys225 230 235 240aca ata aaa ttt gca tca tcc tca gga ggg ggc cta gaa att aca aca 769Thr Ile Lys Phe Ala Ser Ser Ser Gly Gly Gly Leu Glu Ile Thr Thr 245 250 255cat agc ttt aat tgt aga gga gaa ttt ttc tat tgc aat aca tca aac 817His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asn 260 265 270ctg ttt aat agt aca tac atg cct aat ggt aca aaa ggt aat tca aac 865Leu Phe Asn Ser Thr Tyr Met Pro Asn Gly Thr Lys Gly Asn Ser Asn 275 280 285tca acc atc aca atc caa tgc aga ata aaa caa att ata aac atg tgg 913Ser Thr Ile Thr Ile Gln Cys Arg Ile Lys Gln Ile Ile Asn Met Trp 290 295 300cag gag gta gga cga gca atg tat gcc cct ccc att gaa gga aac ata 961Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Glu Gly Asn Ile305 310 315 320acg tgt gaa tcc aat atc aca gga cta cta ttg gta cgt gat gga gga 1009Thr Cys Glu Ser Asn Ile Thr Gly Leu Leu Leu Val Arg Asp Gly Gly 325 330 335aca gag tca aat aat aca gag aca ttc aga cct gga gga gga gat atg 1057Thr Glu Ser Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met 340 345 350agg aac aat tgg aga agt gaa tta tat aaa tat aaa gtg gta gaa att 1105Arg Asn Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile 355 360 365aag cca ttg gga gta gcg ccc act act gca aaa agg aga gtg gtg gag 1153Lys Pro Leu Gly Val Ala Pro Thr Thr Ala Lys Arg Arg Val Val Glu 370 375 380aga gaa aaa aga gca gtg gga ata gga gct gtg ttc ctt ggg ttc ttg 1201Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu385 390 395 400gga gca gca gga agc act atg ggc gcg gca tca atg acg ctg acg gta 1249Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val 405 410 415cag gcc aga caa ttg ttg tct ggt ata gtg caa cag caa agc aat ttg 1297Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu 420 425 430ctg agg gct ata gag gcg caa cag cat ctg ttg caa ctc acg gtc tgg 1345Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp 435 440 445ggc att aag cag ctc cag aca aga gtc ctg gct ata gaa aga tac cta 1393Gly Ile Lys Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu 450 455 460aag gat caa cag ctc cta ggg att tgg ggc cgc tct gga aaa ctc atc 1441Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Arg Ser Gly Lys Leu Ile465 470 475 480tgc acc act aat gta cct tgg aac tcc agc tgg agt aac aga tct caa 1489Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Ser Gln 485 490 495aca gat att tgg gat aac atg acc tgg atg cag tgg gat aga gaa att 1537Thr Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile 500 505 510agt aat tac aca gac aca ata tac agg ttg ctt gaa gac tcg caa aac 1585Ser Asn Tyr Thr Asp Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn 515 520 525cag cag gaa aga aat gaa aaa gat tta tta gca ttg gac agt tgg aaa 1633Gln Gln Glu Arg Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys 530 535 540aat ctg tgg aat tgg ttt agc ata aca aat tgg ctg tgg tat ata aaa 1681Asn Leu Trp Asn Trp Phe Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys545 550 555 560ata ttc ata atg ata gta gga ggc ttg ata ggt ttg aaa ata att ttt 1729Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Lys Ile Ile Phe 565 570 575gct gtg ctc tct ata gtg aat aga gtt agg cag gga tac tca cct tta 1777Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu 580 585 590tcg ttt cag acc cttaccccga acccaggggg acccgacagg ctcgaaagaa 1829Ser Phe Gln Thr 595tcgaaggagg aggtggagag caagacaaag acagatccat tcgcttagtg aacggattct 1889tagcacttgc ctgggacgac tgcggagcct gtgcctcttc agc 1932 2 596 PRT Human immunodeficiency virus HIV-1(D757) 2Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Asn Cys Thr Asn Ala Asn Val Thr Tyr Asp Asn Gly 20 25 30Asn Tyr Thr Glu Glu Ile Lys Asn Cys Ser Phe Asn Thr Thr Thr Glu 35 40 45Leu Arg Asp Gln Lys Gln Lys Val Ala Ala Leu Phe Tyr Lys Leu Asp 50 55 60Val Val Pro Leu Asp Gly Asn Asp Asn Ser Ser Tyr Arg Leu Ile Asn 65 70 75 80Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Asp 85 90 95Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly Tyr Ala Ile Leu Lys 100 105 110Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys His Asn Val Ser 115 120 125Thr Arg Thr Cys Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu 130 135 140Leu Leu Asn Gly Ser Leu Ala Glu Gly Glu Ile Ile Ile Arg Ser Glu145 150 155 160Asn Leu Ala Asn Asn Val Lys Thr Ile Ile Val His Leu Asn Gln Ser 165 170 175Val Arg Ile Val Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile 180 185 190Arg Ile Gly Pro Gly Gln Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly 195 200 205Asp Ile Arg Gln Ala His Cys Asn Ile Ser Glu Gly Lys Trp Asn Glu 210 215 220Thr Leu Gln Arg Val Gly Lys Lys Leu Ala Glu Tyr Phe Pro Asn Lys225 230 235 240Thr Ile Lys Phe Ala Ser Ser Ser Gly Gly Gly Leu Glu Ile Thr Thr 245 250 255His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Asn 260 265 270Leu Phe Asn Ser Thr Tyr Met Pro Asn Gly Thr Lys Gly Asn Ser Asn 275 280 285Ser Thr Ile Thr Ile Gln Cys Arg Ile Lys Gln Ile Ile Asn Met Trp 290 295 300Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Glu Gly Asn Ile305 310 315 320Thr Cys Glu Ser Asn Ile Thr Gly Leu Leu Leu Val Arg Asp Gly Gly 325 330 335Thr Glu Ser Asn Asn Thr Glu Thr Phe Arg Pro Gly Gly Gly Asp Met 340 345 350Arg Asn Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile 355 360 365Lys Pro Leu Gly Val Ala Pro Thr Thr Ala Lys Arg Arg Val Val Glu 370 375 380Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe Leu Gly Phe Leu385 390 395 400Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met Thr Leu Thr Val 405 410 415Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu 420 425 430Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp 435 440 445Gly Ile Lys Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu 450 455 460Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Arg Ser Gly Lys Leu Ile465 470 475 480Cys Thr Thr Asn Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Ser Gln 485 490 495Thr Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile 500 505 510Ser Asn Tyr Thr Asp Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn 515 520 525Gln Gln Glu Arg Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys 530 535 540Asn Leu Trp Asn Trp Phe Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys545 550 555 560Ile Phe Ile Met Ile Val Gly Gly Leu Ile Gly Leu Lys Ile Ile Phe 565 570 575Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu 580 585 590Ser Phe Gln Thr 595 3 1944 DNA Human immunodeficiency virus HIV-1(D747) 3taatgtctgg gcaacacatg cctgtgtacc cacagacccc aacccacaag agatggtttt 60gggaaatgta acagaaaatt ttaacatgtg gagaaatgac atggtgaatc agatgcatga 120ggatgtaatc agt tta tgg gat caa agc cta aag cca tgt gta aag ttg 169 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu 1 5 10acc cca ctc tgt gtc act tta cat tgt aca aat gct acc tat agt aat 217Thr Pro Leu Cys Val Thr Leu His Cys Thr Asn Ala Thr Tyr Ser Asn 15 20 25agt acc tac aat agt acc tac aat gaa gaa ata aaa aat tgc tct ttc 265Ser Thr Tyr Asn Ser Thr Tyr Asn Glu Glu Ile Lys Asn Cys Ser Phe 30 35 40 45aat aca act acg gaa cta aga gat aag aaa cag aaa gta caa gca ctt 313Asn Thr Thr Thr Glu Leu Arg Asp Lys Lys Gln Lys Val Gln Ala Leu 50 55 60ttt tat aaa ctt gat gta gta cca ctt aat act act gat aac tct agt 361Phe Tyr Lys Leu Asp Val Val Pro Leu Asn Thr Thr Asp Asn Ser Ser 65 70 75tat aga tta ata aat tgt aat acc tca gcc ata aca caa gcc tgt cca 409Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro 80 85 90aag gtc tca ttt gac cca att cct ata cat tat tgt gct gga gct ggt 457Lys Val Ser Phe Asp Pro Ile Pro Ile His Tyr Cys Ala Gly Ala Gly 95 100 105tat gcg att cta aag tgt aat aat aag aca ttc aat ggg aca gga cca 505Tyr Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro110 115 120 125tgc cat aat atc agc aca gta caa tgt aca cat gga att aag cca gta 553Cys His Asn Ile Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val 130 135 140gta tca act caa cta ctg tta aat ggt agc cta gca gaa gga gag ata 601Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Gly Glu Ile 145 150 155ata att aga tct gaa aat ctg aca aac aat gtc aaa aca ata ata gta 649Ile Ile Arg Ser Glu Asn Leu Thr Asn Asn Val Lys Thr Ile Ile Val 160 165 170cat ctt aat caa tct gta gaa att gtg tat aca aga ccc aac aat aat 697His Leu Asn Gln Ser Val Glu Ile Val Tyr Thr Arg Pro Asn Asn Asn 175 180 185aca agg aaa ggt gta agg ata gga cca gga caa aca ttc tat gca aca 745Thr Arg Lys Gly Val Arg Ile Gly Pro Gly Gln Thr Phe Tyr Ala Thr190 195 200 205gga gac ata ata gga gac ata aga caa gca cat tgt aac att agt aaa 793Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Lys 210 215 220cat aaa tgg aat gaa act tta caa agg gta ggt aaa aaa tta gca gaa 841His Lys Trp Asn Glu Thr Leu Gln Arg Val Gly Lys Lys Leu Ala Glu 225 230 235cac ttc cct aat aaa aca ata aga ttt gca tca tcc tca gga ggg gac 889His Phe Pro Asn Lys Thr Ile Arg Phe Ala Ser Ser Ser Gly Gly Asp 240 245 250cta gaa att aca aca cat agc ttt aat tgt aga gga gaa ttt ttc tat 937Leu Glu Ile Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr 255 260 265tgc aat aca tca gac ctg ttt aat ggt aca tac atg cct aat ggt aca 985Cys Asn Thr Ser Asp Leu Phe Asn Gly Thr Tyr Met Pro Asn Gly Thr270 275 280 285aaa agt aat tca agc tca acc atc aca att cca tgc aga ata aaa caa 1033Lys Ser Asn Ser Ser Ser Thr Ile Thr Ile Pro Cys Arg Ile Lys Gln 290 295 300att ata aac atg tgg cag gag gta gga cga gca atg tat gcc cct ccc 1081Ile Ile Asn Met Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro 305 310 315att gca gga aac ata acg tgt aaa tcc aat att aca gga ata cta ttg 1129Ile Ala Gly Asn Ile Thr Cys Lys Ser Asn Ile Thr Gly Ile Leu Leu 320 325 330gta cgt gat gga gga ata gag cta aat gat aca aag aca gag aca ttc 1177Val Arg Asp Gly Gly Ile Glu Leu Asn Asp Thr Lys Thr Glu Thr Phe 335 340 345aga ccg gga gga gga gaa atg agg gac aat tgg aga agt gaa tta tat 1225Arg Pro Gly Gly Gly Glu Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr350 355 360 365aaa tat aaa gtg gta gaa att aag cca ttg gga gta gcg ccc act act 1273Lys Tyr Lys Val Val Glu Ile Lys Pro Leu Gly Val Ala Pro Thr Thr 370 375 380gca aaa agg aga gtg gtg gag aga gaa aaa aga gca gtg gga ata gga 1321Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Ile Gly 385 390 395gct gta ttc ctt ggg ttc ttg gga gca gca gga agc act atg ggc gcg 1369Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala 400 405 410gcg tca atg acc gtg acg gta cag gcc aga caa ttg ttg tct ggt ata 1417Ala Ser Met Thr Val Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile 415 420 425gtg caa cag caa agc aat ttg ctg agg gct ata gag gcg caa cag cat 1465Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His430 435 440 445ctg ttg caa ctc acg atc tgg ggg att aag cag ctc cag gca aga gtc 1513Leu Leu Gln Leu Thr Ile Trp Gly Ile Lys Gln Leu Gln Ala Arg Val 450 455 460ctg gct ata gaa aga tac cta aag gaa caa cag ctc cta ggg att tgg 1561Leu Ala Ile Glu Arg Tyr Leu Lys Glu Gln Gln Leu Leu Gly Ile Trp 465 470 475ggc tgc tct gga aaa ctc atc tgc acc act act gta cct tgg aac tcc 1609Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Thr Val Pro Trp Asn Ser 480 485 490agt tgg agt aac aga tct caa aca gat att tgg gat aac atg acc tgg 1657Ser Trp Ser Asn Arg Ser Gln Thr Asp Ile Trp Asp Asn Met Thr Trp 495 500 505atg cag tgg gat aga gaa att agt aat tac aca gaa aca ata tac agg 1705Met Gln Trp Asp Arg Glu Ile Ser Asn Tyr Thr Glu Thr Ile Tyr Arg510 515 520 525ttg ctt gaa gac tcg caa aac cag cag gaa aga aat gaa aaa gat tta 1753Leu Leu Glu Asp Ser Gln Asn Gln Gln Glu Arg Asn Glu Lys Asp Leu 530 535 540tta gca ttg gac agt tgg aaa aat ctg tgg aat tgg ttt agc ata aca 1801Leu Ala Leu Asp Ser Trp Lys Asn Leu Trp Asn Trp Phe Ser Ile Thr 545 550 555aat tgg cta tgg tat ata aaa ata ttc ata ata ata gta gga ggc ttg 1849Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Ile Ile Val Gly Gly Leu 560 565 570ata ggc ttg aga ata att ttt gct gtg ctt tgt ata gta aat aga gtt 1897Ile Gly Leu Arg Ile Ile Phe Ala Val Leu Cys Ile Val Asn Arg Val 575 580 585aag gca gga tac tca cct ttg tcg ttt cag acc cttaccccga accc 1944Lys Ala Gly Tyr Ser Pro Leu Ser Phe Gln Thr590 595 600 4 600 PRT Human immunodeficiency virus HIV-1(D747) 4Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu His Cys Thr Asn Ala Thr Tyr Ser Asn Ser Thr Tyr 20 25 30Asn Ser Thr Tyr Asn Glu Glu Ile Lys Asn Cys Ser Phe Asn Thr Thr 35 40 45Thr Glu Leu Arg Asp Lys Lys Gln Lys Val Gln Ala Leu Phe Tyr Lys 50 55 60Leu Asp Val Val Pro Leu Asn Thr Thr Asp Asn Ser Ser Tyr Arg Leu 65 70 75 80Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Ser 85 90 95Phe Asp Pro Ile Pro Ile His Tyr Cys Ala Gly Ala Gly Tyr Ala Ile 100 105 110Leu Lys Cys Asn Asn Lys Thr Phe Asn Gly Thr Gly Pro Cys His Asn 115 120 125Ile Ser Thr Val Gln Cys Thr His Gly Ile Lys Pro Val Val Ser Thr 130 135 140Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu Gly Glu Ile Ile Ile Arg145 150 155 160Ser Glu Asn Leu Thr Asn Asn Val Lys Thr Ile Ile Val His Leu Asn 165 170 175Gln Ser Val Glu Ile Val Tyr Thr Arg Pro Asn Asn Asn Thr Arg Lys 180 185 190Gly Val Arg Ile Gly Pro Gly Gln Thr Phe Tyr Ala Thr Gly Asp Ile 195 200 205Ile Gly Asp Ile Arg Gln Ala His Cys Asn Ile Ser Lys His Lys Trp 210 215 220Asn Glu Thr Leu Gln Arg Val Gly Lys Lys Leu Ala Glu His Phe Pro225 230 235 240Asn Lys Thr Ile Arg Phe Ala Ser Ser Ser Gly Gly Asp Leu Glu Ile 245 250 255Thr Thr His Ser Phe Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr 260 265 270Ser Asp Leu Phe Asn Gly Thr Tyr Met Pro Asn Gly Thr Lys Ser Asn 275 280 285Ser Ser Ser Thr Ile Thr Ile Pro Cys Arg Ile Lys Gln Ile Ile Asn 290 295 300Met Trp Gln Glu Val Gly Arg Ala Met Tyr Ala Pro Pro Ile Ala Gly305 310 315 320Asn Ile Thr Cys Lys Ser Asn Ile Thr Gly Ile Leu Leu Val Arg Asp 325 330 335Gly Gly Ile Glu Leu Asn Asp Thr Lys Thr Glu Thr Phe Arg Pro Gly 340 345 350Gly Gly Glu Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys 355 360 365Val Val Glu Ile Lys Pro Leu Gly Val Ala Pro Thr Thr Ala Lys Arg 370 375 380Arg Val Val Glu Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Val Phe385 390 395 400Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Met 405 410 415Thr Val Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln 420 425 430Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln 435 440 445Leu Thr Ile Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Ile 450 455 460Glu Arg Tyr Leu Lys Glu Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser465 470 475 480Gly Lys Leu Ile Cys Thr Thr Thr Val Pro Trp Asn Ser Ser Trp Ser 485 490 495Asn Arg Ser Gln Thr Asp Ile Trp Asp Asn Met Thr Trp Met Gln Trp 500 505 510Asp Arg Glu Ile Ser Asn Tyr Thr Glu Thr Ile Tyr Arg Leu Leu Glu 515 520 525Asp Ser Gln Asn Gln Gln Glu Arg Asn Glu Lys Asp Leu Leu Ala Leu 530 535 540Asp Ser Trp Lys Asn Leu Trp Asn Trp Phe Ser Ile Thr Asn Trp Leu545 550 555 560Trp Tyr Ile Lys Ile Phe Ile Ile Ile Val Gly Gly Leu Ile Gly Leu 565 570 575Arg Ile Ile Phe Ala Val Leu Cys Ile Val Asn Arg Val Lys Ala Gly 580 585 590Tyr Ser Pro Leu Ser Phe Gln Thr 595 600 5 1952 DNA Human immunodeficiency virus HIV-1(D760) 5cataatgtct gggctacata tgcctgtgta cccacaggcc ccgacccaca agaaatagtt 60ttggaaaatg taacaggaaa ttttaacatg tggaaaaatg acatggtgga tcaaatgcat 120gaggatgtaa tc agt tta tgg gat caa agc cta aag cca tgt gta aag ttg 171 Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu 1 5 10acc cca ctc tgt gtc act tta gag tgt gga aat gtt aat gct acc aat 219Thr Pro Leu Cys Val Thr Leu Glu Cys Gly Asn Val Asn Ala Thr Asn 15 20 25att acc aat aat ggg gaa aat aat cct acc aat att acc aat aat agg 267Ile Thr Asn Asn Gly Glu Asn Asn Pro Thr Asn Ile Thr Asn Asn Arg 30 35 40 45gaa gaa ata aaa aat tgc cct ttc aat gca acc aca gaa ata aga gat 315Glu Glu Ile Lys Asn Cys Pro Phe Asn Ala Thr Thr Glu Ile Arg Asp 50 55 60agg cag cag aaa gtg tat gca ctt ttt tat aga ctt gat ata gta cca 363Arg Gln Gln Lys Val Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro 65 70 75ctt gat aat aat aat aat agc acc tat aga tta ata aat tgt aat acc 411Leu Asp Asn Asn Asn Asn Ser Thr Tyr Arg Leu Ile Asn Cys Asn Thr 80 85 90tca gcc ata aca caa gcc tgt cca aag gtc act ttt gat cca att cct 459Ser Ala Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Asp Pro Ile Pro 95 100 105ata cac tat tgt gct cca gct ggt tat gcg att cta aag tgt aat aat 507Ile His Tyr Cys Ala Pro Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asn110 115 120 125aag aca ttc aat ggg aca gga cca tgc cat aat gtc agc aca gta caa 555Lys Thr Phe Asn Gly Thr Gly Pro Cys His Asn Val Ser Thr Val Gln 130 135 140tgt aca cat gga att agc cca gtg gta tca act caa cta ctg tta aat 603Cys Thr His Gly Ile Ser Pro Val Val Ser Thr Gln Leu Leu Leu Asn 145 150 155ggt agc cta gca gaa gga gag ata ata att aga tct gaa aat ctg aca 651Gly Ser Leu Ala Glu Gly Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr 160 165 170gac aat gtc aaa aca ata ata gta cat ctt aat caa tct gta gaa gtt 699Asp Asn Val Lys Thr Ile Ile Val His Leu Asn Gln Ser Val Glu Val 175 180 185gtg tgt aca aga ccc aac aat aat aca aga aaa agt ata agg ata gga 747Val Cys Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly190 195 200 205cca gga caa aca ttt tat gca aca gga gac ata ata gga gac ata aga 795Pro Gly Gln Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg 210 215 220caa gca cat tgt aac att agt gaa gat aaa tgg aat gaa act tta caa 843Gln Ala His Cys Asn Ile Ser Glu Asp Lys Trp Asn Glu Thr Leu Gln 225 230 235agg gta ggt aaa aaa cta gca gaa cac ttc cct aat aaa aca ata aaa 891Arg Val Gly Lys Lys Leu Ala Glu His Phe Pro Asn Lys Thr Ile Lys 240 245 250ttt gca gca tcc tca gga ggg gac cta gaa att aca aca tat agt ttt 939Phe Ala Ala Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr Tyr Ser Phe 255 260 265aat tgt aga gga gaa ttt ttc tat tgc aat aca tca ggc ctg ttc aat 987Asn Cys Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn270 275 280 285ggt aca tac atg cct aat ggt aca aaa agt aat tta aac tca acc atc 1035Gly Thr Tyr Met Pro Asn Gly Thr Lys Ser Asn Leu Asn Ser Thr Ile 290 295 300aca atc cca tgc aga ata aaa caa att gtg aac ctg tgg cag gag gta 1083Thr Ile Pro Cys Arg Ile Lys Gln Ile Val Asn Leu Trp Gln Glu Val 305 310 315gga cga gca atg tat gcc cct cca ttt gcc agg aac ata aca tgt aaa 1131Gly Arg Ala Met Tyr Ala Pro Pro Phe Ala Arg Asn Ile Thr Cys Lys 320 325 330tca aat atc aca gga cta cta ttg gta cgt gat gga gga gaa gac aca 1179Ser Asn Ile Thr Gly Leu Leu Leu Val Arg Asp Gly Gly Glu Asp Thr 335 340 345aat gat aca gag ata ttc agt cct gga gga gga gat atg agg gac aat 1227Asn Asp Thr Glu Ile Phe Ser Pro Gly Gly Gly Asp Met Arg Asp Asn350 355 360 365tgg aga agt gaa tta tac aaa tat aaa gtg gta gaa att aag cca ttg 1275Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys Pro Leu 370 375 380gga gta gca ccc act aca gca aaa agg aga gtg gtg gag aga gaa aaa 1323Gly Val Ala Pro Thr Thr Ala Lys Arg Arg Val Val Glu Arg Glu Lys 385 390 395aga gca gtg gga tta gga gct gtg ttc ctt ggg ttc ttg gga gca gca 1371Arg Ala Val Gly Leu Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala 400 405 410gga agc act atg ggc gcg gcg tca ata acg ctg acg gta cag gcc aga 1419Gly Ser Thr Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg 415 420 425caa tta ctg tct ggt ata gtg caa cag caa agc aat ttg ctg agg gct 1467Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala430 435 440 445ata gag gcg caa cag cat ctg ttg caa ctc acg gtc tgg ggc att aag 1515Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys 450 455 460cag ctc cag aca aga gtc ctg gct ata gaa aga tac cta aag gat caa 1563Gln Leu Gln Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu Lys Asp Gln 465 470 475cag ctc cta ggg atg tgg ggc tgc tct gga aaa ctc atc tgc acc act 1611Gln Leu Leu Gly Met Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr 480 485 490gct gta cct tgg aac tcc agt tgg agt aac aga tct caa aca gat att 1659Ala Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Ser Gln Thr Asp Ile 495 500 505tgg gat aac atg acc tgg atg cag tgg gat agg gaa att agt aat tac 1707Trp Asp Asn Met Thr Trp Met Gln Trp Asp Arg Glu Ile Ser Asn Tyr510 515 520 525aca aat aca ata tac agg ttg ctt gaa gac tcg caa aac cag cag gaa 1755Thr Asn Thr Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn Gln Gln Glu 530 535 540aga aat gaa aaa gat tta tta gca ttg gac agt tgg aaa aat ctg tgg 1803Arg Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys Asn Leu Trp 545 550 555aat tgg ttt agc ata aca aat tgg ctg tgg tat ata aaa ata ttc ata 1851Asn Trp Phe Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile 560 565 570atg ata gta gga ggc ttg ata ggt ttg aga ata att ttt gct gtg ctc 1899Met Ile Val Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala Val Leu 575 580 585tct ata gtg aat aga gtt agg cag gga tac tca cct ttg tcg ttt cag 1947Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln590 595 600 605acc ct 1952Thr 6 606 PRT Human immunodeficiency virus HIV-1(D760) 6Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Glu Cys Gly Asn Val Asn Ala Thr Asn Ile Thr Asn 20 25 30Asn Gly Glu Asn Asn Pro Thr Asn Ile Thr Asn Asn Arg Glu Glu Ile 35 40 45Lys Asn Cys Pro Phe Asn Ala Thr Thr Glu Ile Arg Asp Arg Gln Gln 50 55 60Lys Val Tyr Ala Leu Phe Tyr Arg Leu Asp Ile Val Pro Leu Asp Asn 65 70 75 80Asn Asn Asn Ser Thr Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile 85 90 95Thr Gln Ala Cys Pro Lys Val Thr Phe Asp Pro Ile Pro Ile His Tyr 100 105 110Cys Ala Pro Ala Gly Tyr Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe 115 120 125Asn Gly Thr Gly Pro Cys His Asn Val Ser Thr Val Gln Cys Thr His 130 135 140Gly Ile Ser Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu145 150 155 160Ala Glu Gly Glu Ile Ile Ile Arg Ser Glu Asn Leu Thr Asp Asn Val 165 170 175Lys Thr Ile Ile Val His Leu Asn Gln Ser Val Glu Val Val Cys Thr 180 185 190Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gly Pro Gly Gln 195 200 205Thr Phe Tyr Ala Thr Gly Asp Ile Ile Gly Asp Ile Arg Gln Ala His 210 215 220Cys Asn Ile Ser Glu Asp Lys Trp Asn Glu Thr Leu Gln Arg Val Gly225 230 235 240Lys Lys Leu Ala Glu His Phe Pro Asn Lys Thr Ile Lys Phe Ala Ala 245 250 255Ser Ser Gly Gly Asp Leu Glu Ile Thr Thr Tyr Ser Phe Asn Cys Arg 260 265 270Gly Glu Phe Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Gly Thr Tyr 275 280 285Met Pro Asn Gly Thr Lys Ser Asn Leu Asn Ser Thr Ile Thr Ile Pro 290 295 300Cys Arg Ile Lys Gln Ile Val Asn Leu Trp Gln Glu Val Gly Arg Ala305 310 315 320Met Tyr Ala Pro Pro Phe Ala Arg Asn Ile Thr Cys Lys Ser Asn Ile 325 330 335Thr Gly Leu Leu Leu Val Arg Asp Gly Gly Glu Asp Thr Asn Asp Thr 340 345 350Glu Ile Phe Ser Pro Gly Gly Gly Asp Met Arg Asp Asn Trp Arg Ser 355 360 365Glu Leu Tyr Lys Tyr Lys Val Val Glu Ile Lys Pro Leu Gly Val Ala 370 375 380Pro Thr Thr Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg Ala Val385 390 395 400Gly Leu Gly Ala Val Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr 405 410 415Met Gly Ala Ala Ser Ile Thr Leu Thr Val Gln Ala Arg Gln Leu Leu 420 425 430Ser Gly Ile Val Gln Gln Gln Ser Asn Leu Leu Arg Ala Ile Glu Ala 435 440 445Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln 450 455 460Thr Arg Val Leu Ala Ile Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu465 470 475 480Gly Met Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro 485 490 495Trp Asn Ser Ser Trp Ser Asn Arg Ser Gln Thr Asp Ile Trp Asp Asn 500 505 510Met Thr Trp Met Gln Trp Asp Arg Glu Ile Ser Asn Tyr Thr Asn Thr 515 520 525Ile Tyr Arg Leu Leu Glu Asp Ser Gln Asn Gln Gln Glu Arg Asn Glu 530 535 540Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys Asn Leu Trp Asn Trp Phe545 550 555 560Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val 565 570 575Gly Gly Leu Ile Gly Leu Arg Ile Ile Phe Ala Val Leu Ser Ile Val 580 585 590Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr 595 600 605 7 9 PRT Human immunodeficiency virus 7Met Pro Asn Gly Thr Lys Ser Asn Ser 1 5 8 9 PRT Human immunodeficiency virus 8Met Pro Asn Gly Thr Lys Gly Asn Ser 1 5 9 9 PRT Human immunodeficiency virus 9Met Pro Asn Gly Thr Lys Ser Asn Leu 1 5 10 14 PRT Human immunodeficiency virus 10Arg Asn Glu Lys Asp Leu Leu Ala Leu Asp Ser Trp Lys Asn 1 5 10 11 615 PRT Human immunodeficiency virus HIV-1(Bru) 11Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Ser Leu Lys Cys Thr Asp Leu Gly Asn Ala Thr Asn Thr Asn 20 25 30Ser Ser Asn Thr Asn Ser Ser Ser Gly Glu Met Met Met Glu Lys Gly 35 40 45Glu Ile Lys Asn Cys Ser Phe Asn Ile Ser Thr Ser Ile Arg Gly Lys 50 55 60Val Gln Lys Glu Tyr Ala Phe Phe Tyr Lys Leu Asp Ile Ile Pro Ile 65 70 75 80Asp Asn Asp Thr Thr Ser Tyr Thr Leu Thr Ser Cys Asn Thr Ser Val 85 90 95Ile Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His 100 105 110Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr 115 120 125Phe Asn Gly Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr 130 135 140His Gly Ile Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser145 150 155 160Leu Ala Glu Glu Glu Val Val Ile Arg Ser Ala Asn Phe Thr Asp Asn 165 170 175Ala Lys Thr Ile Ile Val Gln Leu Asn Gln Ser Val Glu Ile Asn Cys 180 185 190Thr Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Arg Ile Gln Arg Gly 195 200 205Pro Gly Arg Ala Phe Val Thr Ile Gly Lys Ile Gly Asn Met Arg Gln 210 215 220Ala His Cys Asn Ile Ser Arg Ala Lys Trp Asn Ala Thr Leu Lys Gln225 230 235 240Ile Ala Ser Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Ile 245 250 255Phe Lys Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Thr His Ser Phe 260 265 270Asn Cys Gly Gly Glu Phe Phe Tyr Cys Asn Ser Thr Gln Leu Phe Asn 275 280 285Ser Thr Trp Phe Asn Ser Thr Trp Ser Thr Glu Gly Ser Asn Asn Thr 290 295 300Glu Gly Ser Asp Thr Ile Thr Leu Pro Cys Arg Ile Lys Gln Phe Ile305 310 315 320Asn Met Trp Gln Glu Val Gly Lys Ala Met Tyr Ala Pro Pro Ile Ser 325 330 335Gly Gln Ile Arg Cys Ser Ser Asn Ile Thr Gly Leu Leu Leu Thr Arg 340 345 350Asp Gly Gly Asn Asn Asn Asn Gly Ser Glu Ile Phe Arg Pro Gly Gly 355 360 365Gly Asp Met Arg Asp Asn Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val 370 375 380Val Lys Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg385 390 395 400Val Val Gln Arg Glu Lys Arg Ala Val Gly Ile Gly Ala Leu Phe Leu 405 410 415Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser Met Thr 420 425 430Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln 435 440 445Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu 450 455 460Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu465 470 475 480Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly 485 490 495Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn 500 505 510Lys Ser Leu Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu Trp Asp 515 520 525Arg Glu Ile Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu 530 535 540Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp545 550 555 560Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp Leu Trp 565 570 575Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg 580 585 590Ile Val Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr 595 600 605Ser Pro Leu Ser Phe Gln Thr 610 615 12 610 PRT Human immunodeficiency virus HIV-1(SF2) 12Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Asn Cys Thr Asp Leu Gly Lys Ala Thr Asn Thr Asn 20 25 30Ser Ser Asn Trp Lys Glu Glu Ile Lys Gly Glu Ile Lys Asn Cys Ser 35 40 45Phe Asn Ile Thr Thr Ser Ile Arg Asp Lys Ile Gln Lys Glu Asn Ala 50 55 60Leu Phe Arg Asn Leu Asp Val Val Pro Ile Asp Asn Ala Ser Thr Thr 65 70 75 80Thr Asn Tyr Thr Asn Tyr Arg Leu Ile His Cys Asn Arg Ser Val Ile 85 90 95Thr Gln Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr 100 105 110Cys Thr Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asn Lys Thr Phe 115 120 125Asn Gly Lys Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His 130 135 140Gly Ile Arg Pro Ile Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu145 150 155 160Ala Glu Glu Glu Val Val Ile Arg Ser Asp Asn Phe Thr Asn Asn Ala 165 170 175Lys Thr Ile Ile Val Gln Leu Asn Glu Ser Val Ala Ile Asn Cys Thr 180 185 190Arg Pro Asn Asn Asn Thr Arg Lys Ser Ile Tyr Ile Gly Pro Gly Arg 195 200 205Ala Phe His Thr Thr Gly Arg Ile Ile Gly Asp Ile Arg Lys Ala His 210 215 220Cys Asn Ile Ser Arg Ala Gln Trp Asn Asn Thr Leu Glu Gln Ile Val225 230 235 240Lys Lys Leu Arg Glu Gln Phe Gly Asn Asn Lys Thr Ile Val Phe Asn 245 250 255Gln Ser Ser Gly Gly Asp Pro Glu Ile Val Met His Ser Phe Asn Cys 260 265 270Arg Gly Glu Phe Phe Tyr Cys Asn Thr Thr Gln Leu Phe Asn Asn Thr 275 280 285Trp Arg Leu Asn His Thr Glu Gly Thr Lys Gly Asn Asp Thr Ile Ile 290 295 300Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln Glu Val Gly305 310 315 320Lys Ala Met Tyr Ala Pro Pro Ile Gly Gly Gln Ile Ser Cys Ser Ser 325 330 335Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Thr Asn Val Thr 340 345 350Asn Asp Thr Glu Val Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn 355 360 365Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Ile Lys Ile Glu Pro Leu 370 375 380Gly Ile Ala Pro Thr Lys Ala Lys Arg Arg Val Val Gln Arg Glu Lys385 390 395 400Arg Ala Val Gly Ile Val Gly Ala Met Phe Leu Gly Phe Leu Gly Ala 405 410 415Ala Gly Ser Thr Met Gly Ala Val Ser Leu Thr Leu Thr Val Gln Ala 420 425 430Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg 435 440 445Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile 450 455 460Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr Leu Arg Asp465 470 475 480Gln Gln Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys Leu Ile Cys Thr 485 490 495Thr Ala Val Pro Trp Asn Ala Ser Trp Ser Asn Lys Ser Leu Glu Asp 500 505 510Ile Trp Asp Asn Met Thr Trp Met Gln Trp Glu Arg Glu Ile Asp Asn 515 520 525Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser Gln Asn Gln Gln 530 535 540Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu545 550 555 560Trp Asn Trp Phe Ser Ile Thr Asn Trp Leu Trp Tyr Ile Lys Ile Phe 565 570 575Ile Met Ile Val Gly Gly Leu Val Gly Leu Arg Ile Val Phe Ala Val 580 585 590Leu Ser Ile Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe 595 600 605Gln Thr 610 13 608 PRT Human immunodeficiency virus HIV-1(Eli) 13Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Asn Cys Ser Asp Glu Leu Arg Asn Asn Gly Thr Met 20 25 30Gly Asn Asn Val Thr Thr Glu Glu Lys Gly Met Lys Asn Cys Ser Phe 35 40 45Asn Val Thr Thr Val Leu Lys Asp Lys Lys Gln Gln Val Tyr Ala Leu 50 55 60Phe Tyr Arg Leu Asp Ile Val Pro Ile Asp Asn Asp Ser Ser Thr Asn 65 70 75 80Ser Thr Asn Tyr Arg Leu Ile Asn Cys Asn Thr Ser Ala Ile Thr Gln 85 90 95Ala Cys Pro Lys Val Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala 100 105 110Pro Ala Gly Phe Ala Ile Leu Lys Cys Arg Asp Lys Lys Phe Asn Gly 115 120 125Thr Gly Pro Cys Thr Asn Val Ser Thr Val Gln Cys Thr His Gly Ile 130 135 140Arg Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly Ser Leu Ala Glu145 150 155 160Glu Glu Val Ile Ile Arg Ser Glu Asn Leu Thr Asn Asn Ala Lys Asn 165 170 175Ile Ile Ala His Leu Asn Glu Ser Val Lys Ile Thr Cys Ala Arg Pro 180 185 190Tyr Gln Asn Thr Arg Gln Arg Thr Pro Ile Gly Leu Gly Gln Ser Leu 195 200 205Tyr Thr Thr Arg Ser Arg Ser Ile Ile Gly Gln Ala His Cys Asn Ile 210 215 220Ser Arg Ala Gln Trp Ser Lys Thr Leu Gln Gln Val Ala Arg Lys Leu225 230 235 240Gly Thr Leu Leu Asn Lys Thr Ile Ile Lys Phe Lys Pro Ser Ser Gly 245 250 255Gly Asp Pro Glu Ile Thr Thr His Ser Phe Asn Cys Gly Gly Glu Phe 260 265 270Phe Tyr Cys Asn Thr Ser Gly Leu Phe Asn Ser Thr Trp Asn Ile Ser 275 280 285Ala Trp Asn Asn Ile Thr Glu Ser Asn Asn Ser Thr Asn Thr Asn Ile 290 295 300Thr Leu Gln Cys Arg Ile Lys Gln Ile Ile Lys Met Val Ala Gly Arg305 310 315 320Lys Ala Ile Tyr Ala Pro Pro Ile Glu Arg Asn Ile Leu Cys Ser Ser 325 330 335Asn Ile Thr Gly Leu Leu Leu Thr Arg Asp Gly Gly Ile Asn Asn Ser 340 345 350Thr Asn Glu Thr Phe Arg Pro Gly Gly Gly Asp Met Arg Asp Asn Trp 355 360 365Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Gln Ile Glu Pro Leu Gly 370 375 380Val Ala Pro Thr Arg Ala Lys Arg Arg Val Val Glu Arg Glu Lys Arg385 390 395 400Ala Ile Gly Leu Gly Ala Met Phe Leu Gly Phe Leu Gly Ala Ala Gly 405 410 415Ser Thr Met Gly Ala Arg Ser Val Thr Leu Thr Val Gln Ala Arg Gln 420 425 430Leu Met Ser Gly Ile Val Gln Gln Gln Asn Asn Leu Leu Arg Ala Ile 435 440 445Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val Trp Gly Ile Lys Gln 450 455 460Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln465 470 475 480Leu Leu Gly Ile Trp Gly Cys Ser Gly Lys His Ile Cys Thr Thr Asn 485 490 495Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Ser Leu Asn Glu Ile Trp 500 505 510Gln Asn Met Thr Trp Met Glu Trp Glu Arg Glu Ile Asp Asn Tyr Thr 515 520 525Gly Leu Ile Tyr Ser Leu Ile Glu Glu Ser Gln Thr Gln Gln Glu Lys 530 535 540Asn Glu Lys Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu Trp Asn545 550 555 560Trp Phe Ser Ile Thr Gln Trp Leu Trp Tyr Ile Lys Ile Phe Ile Met 565 570 575Ile Ile Gly Gly Leu Ile Gly Leu Arg Ile Val Phe Ala Val Leu Ser 580 585 590Leu Val Asn Arg Val Arg Gln Gly Tyr Ser Pro Leu Ser Phe Gln Thr 595 600 605 14 613 PRT Human immunodeficiency virus HIV-1(Mal) 14Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Asn Cys Thr Asn Val Asn Gly Thr Ala Val Asn Gly 20 25 30Thr Asn Ala Gly Ser Asn Arg Thr Asn Ala Glu Leu Lys Met Glu Ile 35 40 45Gly Glu Val Lys Asn Cys Ser Phe Asn Ile Thr Pro Val Gly Ser Asp 50 55 60Lys Arg Gln Glu Tyr Ala Thr Phe Tyr Asn Leu Asp Leu Val Gln Ile 65 70 75 80Asp Asp Ser Asp Asn Ser Ser Tyr Arg Leu Ile Asn Cys Asn Thr Ser 85 90 95Val Ile Thr Gln Ala Cys Pro Lys Val Thr Phe Asp Pro Ile Pro Ile 100 105 110His Tyr Cys Ala Pro Ala Gly Phe Ala Ile Leu Lys Cys Asn Asp Lys 115 120 125Lys Phe Asn Gly Thr Glu Ile Cys Lys Asn Val Ser Thr Val Gln Cys 130 135 140Thr His Gly Ile Lys Pro Val Val Ser Thr Gln Leu Leu Leu Asn Gly145 150 155 160Ser Leu Ala Glu Glu Glu Ile Met Ile Arg Ser Glu Asn Leu Thr Asp 165 170 175Asn Thr Lys Asn Ile Ile Val Gln Leu Asn Glu Thr Val Thr Ile Asn 180 185 190Cys Thr Arg Pro Gly Asn Asn Thr Arg Arg Gly Ile His Phe Gly Pro 195 200 205Gly Gln Ala Leu Tyr Thr Thr Gly Ile Val Gly Asp Ile Arg Arg Ala 210 215 220Tyr Cys Thr Ile Asn Glu Thr Glu Trp Asp Lys Thr Leu Gln Gln Val225 230 235 240Ala Val Lys Leu Gly Ser Leu Leu Asn Lys Thr Lys Ile Ile Phe Asn 245 250 255Ser Ser Ser Gly Gly Asp Pro Glu Ile Thr Thr His Ser Phe Asn Cys 260 265 270Arg Gly Glu Phe Phe Tyr Cys Asn Thr Ser Lys Leu Phe Asn Ser Thr 275 280 285Trp Gln Asn Asn Gly Ala Arg Leu Ser Asn Ser Thr Glu Ser Thr Gly 290 295 300Ser Ile Thr Leu Pro Cys Arg Ile Lys Gln Ile Ile Asn Met Trp Gln305 310 315 320Lys Thr Gly Lys Ala Met Tyr Ala Pro Pro Ile Ala Gly Val Ile Asn 325 330 335Cys Leu Ser Asn Ile Thr Gly Leu Ile Leu Thr Arg Asp Gly Gly Asn 340 345 350Ser Ser Asp Asn Ser Asp Asn Glu Thr Leu Arg Pro Gly Gly Gly Asp 355 360 365Met Arg Asp Asn Trp Ile Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg 370 375 380Ile Glu Pro Leu Gly Val Ala Pro Thr Lys Ala Lys Arg Arg Val Val385 390 395 400Glu Arg Glu Lys Arg Ala Ile Gly Leu Gly Ala Met Phe Leu Gly Phe 405 410 415Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ser Leu Thr Leu Thr 420 425 430Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln Gln Gln Asn Asn 435 440 445Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu Thr Val 450 455 460Trp Gly Ile Lys Gln Leu Gln Ala Arg Val Leu Ala Val Glu Arg Tyr465 470 475 480Leu Gln Asp Gln Arg Leu Leu Gly Met Trp Gly Cys Ser Gly Lys His 485 490 495Ile Cys Thr Thr Phe Val Pro Trp Asn Ser Ser Trp Ser Asn Arg Ser 500 505 510Leu Asp Asp Ile Trp Asn Asn Met Thr Trp Met Gln Trp Glu Lys Glu 515 520 525Ile Ser Asn Tyr Thr Gly Ile Ile Tyr Asn Leu Ile Glu Glu Ser Gln 530 535 540Ile Gln Gln Glu Lys Asn Glu Lys Glu Leu Leu Glu Leu Asp Lys Trp545 550 555 560Ala Ser Leu Trp Asn Trp Phe Ser Ile Ser Lys Trp Leu Trp Tyr Ile 565 570 575Arg Ile Phe Ile Ile Val Val Gly Gly Leu Ile Gly Leu Arg Ile Ile 580 585 590Phe Ala Val Leu Ser Leu Val Asn Arg Val Arg Gln Gly Tyr Ser Pro 595 600 605Leu Ser Leu Gln Thr 610 15 602 PRT Simian immunodeficiency virus SIVcpz 15Ser Leu Trp Asp Gln Ser Leu Lys Pro Cys Val Lys Leu Thr Pro Leu 1 5 10 15Cys Val Thr Leu Gln Cys Ser Lys Ala Asn Phe Ser Gln Ala Lys Asn 20 25 30Leu Thr Asn Gln Thr Ser Ser Pro Pro Leu Glu Met Lys Asn Cys Ser 35 40 45Phe Asn Val Thr Thr Glu Leu Arg Asp Lys Lys Lys Gln Val Tyr Ser 50 55 60Leu Phe Tyr Val Glu Asp Val Val Asn Leu Gly Asn Glu Asn Asn Thr 65 70 75 80Tyr Arg Ile Ile Asn Cys Asn Thr Thr Ala Ile Thr Gln Ala Cys Pro 85 90 95Lys Thr Ser Phe Glu Pro Ile Pro Ile His Tyr Cys Ala Pro Ala Gly 100 105 110Phe Ala Ile Leu Lys Cys Asn Asp Lys Asp Phe Ser Gly Lys Gly Lys 115 120 125Cys Thr Asn Val Ser Thr Val His Cys Thr His Gly Ile Lys Pro Val 130 135 140Val Thr Thr Gln Leu Leu Ile Asn Gly Ser Leu Ala Glu Gly Asn Ile145 150 155 160Thr Val Arg Val Glu Asn Lys Ser Lys Asn Thr Asp Val Trp Ile Val 165 170 175Gln Leu Val Glu Ala Val Ser Leu Asn Cys His Arg Pro Gly Asn Asn 180 185 190Thr Arg Gly Glu Val Gln Ile Gly Pro Gly Met Thr Phe Tyr Asn Ile 195 200 205Glu Asn Val Val Gly Asp Thr Arg Ser Ala Tyr Cys Lys Ile Asn Gly 210 215 220Thr Thr Trp Asn Arg Thr Val Glu Glu Val Lys Lys Ala Leu Ala Thr225 230 235 240Ser Ser Asn Arg Thr Ala Ala Asn Ile Thr Leu Asn Arg Ala Ser Gly 245 250 255Gly Asp Pro Glu Val Thr His His Met Phe Asn Cys Gly Gly Glu Phe 260 265 270Phe Tyr Cys Asn Thr Ser Gln Ile Phe Thr Asp Asn Ile Thr Asn Gly 275 280 285Ile Ile Ile Leu Pro Cys Arg Ile Arg Gln Ile Val Ser Ser Trp Met 290 295 300Arg Val Gly Arg Gly Ile Tyr Ala Pro Pro Ile Arg Gly Asn Ile Thr305 310 315 320Cys Asn Ser Asn Ile Thr Gly Leu Leu Leu Thr Ser Asp Thr Pro Val 325 330 335Thr Asn Asn Ser Gly Asn Leu Thr Phe Arg Pro Thr Gly Gly Asn Met 340 345 350Lys Asp Ile Trp Arg Ser Glu Leu Tyr Lys Tyr Lys Val Val Arg Ile 355 360 365Glu Pro Leu Ser Val Ala Pro Thr Lys Ala Arg Arg His Thr Val Ala 370 375 380Arg Gln Lys Asp Arg Gln Lys Arg Ala Ala Phe Gly Leu Gly Ala Leu385 390 395 400Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Ala Ala 405 410 415Val Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln 420 425 430Gln Gln Asn Asn Leu Leu Lys Ala Ile Glu Ala Gln Gln His Leu Leu 435 440 445Gln Leu Ser Ile Trp Gly Val Lys Gln Leu Gln Ala Arg Leu Leu Ala 450 455 460Val Glu Arg Tyr Leu Gln Asp Gln Gln Ile Leu Gly Leu Trp Gly Cys465 470 475 480Ser Gly Lys Ala Val Cys Tyr Thr Thr Val Pro Trp Asn Asn Ser Trp 485 490 495Pro Gly Ser Asn Ser Thr Asp Asp Ile Trp Gly Asn Leu Thr Trp Gln 500 505 510Gln Trp Asp Lys Leu Val Ser Asn Tyr Thr Gly Lys Ile Phe Gly Leu 515 520 525Leu Glu Glu Ala Gln Ser Gln Gln Glu Lys Asn Glu Arg Asp Leu Leu 530 535 540Glu Leu Asp Gln Trp Ala Ser Leu Trp Asn Trp Phe Asp Ile Thr Lys545 550 555 560Trp Leu Trp Tyr Ile Lys Ile Phe Leu Met Ala Val Gly Gly Ile Ile 565 570 575Gly Leu Arg Ile Ile Met Thr Val Phe Ser Val Val Arg Arg Val Arg 580 585 590Gln Gly Tyr Ser Pro Leu Ser Leu Gln Thr 595 600

Claims

1. A peptide having antigenic properties, wherein the peptide is a sub-peptide of amino acids 294-321 of SEQ ID NO:2, amino acids 296-323 of SEQ ID NO:4, or amino acids 304-331 of SEQ ID NO:6, wherein the sub-peptide includes the sequence NXT or NXS, and wherein the sub-peptide has a length of at least 7 amino acids.

2. The peptide according to claim 1, produced from an HIV-1 isolate selected from the group consisting of the virus HIV-1D757, the virus HIV-1D747, the virus HIV-1D760, or a combination, thereof.

3. The peptide according to claim 2, produced from the virus HIV-1D757.

4. The peptide according to claim 2, produced from the virus HIV-1D747.

5. The peptide according to claim 2, produced from the virus HIV-1D760.

6. The peptide according to claim 1, produced by chemical synthesis.

7. A process for producing antibodies comprising injecting an animal with the peptide according to claim 1, and recovering the antibodies produced by the animal in response to the peptide.