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
Research Project (R01)
Project #
2R01AI025328-09
Application #
3569134
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1987-09-01
Project End
2001-03-31
Budget Start
1996-04-01
Budget End
1997-03-31
Support Year
9
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Stansell, Elizabeth; Panico, Maria; Canis, Kevin et al. (2015) Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate. PLoS One 10:e0124784
Postler, Thomas S; Bixby, Jacqueline G; Desrosiers, Ronald C et al. (2014) Systematic analysis of intracellular trafficking motifs located within the cytoplasmic domain of simian immunodeficiency virus glycoprotein gp41. PLoS One 9:e114753
Westmoreland, Susan V; Converse, A Peter; Hrecka, Kasia et al. (2014) SIV vpx is essential for macrophage infection but not for development of AIDS. PLoS One 9:e84463
Postler, Thomas S; Desrosiers, Ronald C (2012) The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-?B activation through TGF-?-activated kinase 1. Cell Host Microbe 11:181-93
Postler, Thomas S; Martinez-Navio, José M; Yuste, Eloísa et al. (2012) Evidence against extracellular exposure of a highly immunogenic region in the C-terminal domain of the simian immunodeficiency virus gp41 transmembrane protein. J Virol 86:1145-57
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
Stansell, Elizabeth; Canis, Kevin; Haslam, Stuart M et al. (2011) Simian immunodeficiency virus from the sooty mangabey and rhesus macaque is modified with O-linked carbohydrate. J Virol 85:582-95
Stansell, Elizabeth; Desrosiers, Ronald C (2010) Fundamental difference in the content of high-mannose carbohydrate in the HIV-1 and HIV-2 lineages. J Virol 84:8998-9009
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

Showing the most recent 10 out of 79 publications