Mechanisms of Cell Signaling by the Human Cytomegalovirus US27 Gene Product

Information

  • Research Project
  • 7456241
  • ApplicationId
    7456241
  • Core Project Number
    R15AI074029
  • Full Project Number
    1R15AI074029-01A1
  • Serial Number
    74029
  • FOA Number
    PA-06-42
  • Sub Project Id
  • Project Start Date
    2/1/2008 - 17 years ago
  • Project End Date
    1/31/2011 - 14 years ago
  • Program Officer Name
    BEISEL, CHRISTOPHER E.
  • Budget Start Date
    2/1/2008 - 17 years ago
  • Budget End Date
    1/31/2011 - 14 years ago
  • Fiscal Year
    2008
  • Support Year
    1
  • Suffix
    A1
  • Award Notice Date
    1/14/2008 - 17 years ago

Mechanisms of Cell Signaling by the Human Cytomegalovirus US27 Gene Product

[unreadable] DESCRIPTION (provided by applicant): Human cytomegalovirus (HCMV) is a widespread pathogen that has devised numerous mechanisms for evading the host immune system. One such strategy involves molecular mimicry, the expression of proteins that functionally resemble host proteins. The US27 gene product is a predicted G-protein coupled receptor with homology to human chemokine receptors. The specific goals of this research application are to investigate the impact of this receptor on cell growth and survival, identify ligands that bind US27, and characterize downstream signaling events with the aim of understanding how this virally encoded receptor exploits cell signaling for the advantage of the virus. We hypothesize that US27 functions to alter communication between immune cells during virus infection by interfering with normal chemokine signaling. This is based on the observations the US27 gene product contains many features common to cellular chemokine receptors and the finding that US27 is expressed in HCMV infected cells and present in the envelope of infectious virions. While the US27 gene is non-essential for lytic replication in vitro, this may indicate a role in other aspects of HCMV infection in vivo, such as immune modulation, pathogenesis, or dissemination. The proposed study will provide a thorough characterization of this viral GPCR. We will a) examine the ability of US27 to induce cell cycle arrest or trigger apoptosis, b) identify US27 ligands using receptor chimeras to screen a library of human chemokines, and c) elucidate cell signaling pathways employed by US27. The results of these studies will provide a better understanding of the molecular action of US27, leading to future studies that may clarify the role of this protein in virus infection and provide a potential target for novel anti-viral therapeutics. PUBLIC HEALTH RELEVANCE: Opportunistic pathogens like human cytomegalovirus (HCMV) can cause serious disease in individuals with compromised immune systems, such as transplant recipients, AIDS patients, or newborn infants. HCMV infects 70-90% of the general population, causing pneumonitis, retinitis, and congenital defects, and it has also been implicated in the acceleration of cardiovascular disease. By studying the molecular interactions between this pathogen and its human host, novel antiviral drug targets may be identified, potentially leading to decreased human mortality and disease. [unreadable] [unreadable] [unreadable]

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R15
  • Administering IC
    AI
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    212321
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    855
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIAID:212321\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF SAN FRANCISCO
  • Organization Department
    BIOLOGY
  • Organization DUNS
    078770294
  • Organization City
    SAN FRANCISCO
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    941171080
  • Organization District
    UNITED STATES