Abstract

SIV infection of rhesus monkeys mimics many of the features of HIV induced disease in humans. The virus targets CD4+ T lymphocytes, viral replication is persistent despite an apparently strong host immune response and infection leads to gradual declines in CD4+ lymphocyte concentrations and death. The long-term goal of the proposed studies is to understand the molecular mechanisms of AIDS disease process in as great detail as possible using the experimental SIV system. The current proposal focuses on the role of the nef gene and the need for lymphocyte activation for viral replication. Recent studies from this investigator's laboratory suggest that Nef may activate signal transduction pathways causing lymphocyte activation and thus greatly facilitate virus replication in vivo. To obtain more definitive evidence for the role of Nef in viral infection, the following specific aims are proposed:
Specific Aim 1 : To relate SIV Nef sequence to function.
Specific Aim 2 : To select HIV variants that cause lymphocyte activation.
Specific Aim 3 : To investigate the mechanisms of Nef-induced lymphocytes activation.
Specific Aim 4 : To provide in vivo evidence for Nef-induced lymphocyte activation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI025328-11
Application #
2671907
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1987-09-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Martinez-Navio, Jose M; Desrosiers, Ronald C (2012) Neutralizing capacity of monoclonal antibodies that recognize peptide sequences underlying the carbohydrates on gp41 of simian immunodeficiency virus. J Virol 86:12484-93
Yuste, Eloisa; Bixby, Jacqueline; Lifson, Jeffrey et al. (2008) Glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can be targets for neutralizing antibodies. J Virol 82:12472-86
Laird, Melissa E; Igarashi, Tatsuhiko; Martin, Malcolm A et al. (2008) Importance of the V1/V2 loop region of simian-human immunodeficiency virus envelope glycoprotein gp120 in determining the strain specificity of the neutralizing antibody response. J Virol 82:11054-65
Mansfield, Keith; Lang, Sabine M; Gauduin, Marie-Claire et al. (2008) Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. J Virol 82:4135-48
Sato, Shuji; Yuste, Eloisa; Lauer, William A et al. (2008) Potent antibody-mediated neutralization and evolution of antigenic escape variants of simian immunodeficiency virus strain SIVmac239 in vivo. J Virol 82:9739-52
Laird, Melissa E; Desrosiers, Ronald C (2007) Infectivity and neutralization of simian immunodeficiency virus with FLAG epitope insertion in gp120 variable loops. J Virol 81:10838-48
Pikora, Cheryl A; Wittish, Christine; Desrosiers, Ronald C (2006) p6gag of human and simian immunodeficiency viruses is tolerant to small in-frame deletions downstream of the late domain. Virology 346:479-89
Pikora, Cheryl; Wittish, Christine; Desrosiers, Ronald C (2005) Identification of two N-linked glycosylation sites within the core of the simian immunodeficiency virus glycoprotein whose removal enhances sensitivity to soluble CD4. J Virol 79:12575-83
Swigut, Tomek; Alexander, Louis; Morgan, Jennifer et al. (2004) Impact of Nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus. J Virol 78:13335-44
Alexander, Louis; Illyinskii, Petr O; Lang, Sabine M et al. (2003) Determinants of increased replicative capacity of serially passaged simian immunodeficiency virus with nef deleted in rhesus monkeys. J Virol 77:6823-35

Showing the most recent 10 out of 69 publications