In this application, the authors seek to evaluate chimeric simian-human immunodeficiency virus (SHIV) infection of monkeys, which has been demonstrated to be applicable to studies aimed at examining the impact of env variation and viral replication and pathogenesis in vivo. The investigators have derived a pathogenic SHIV, 33A, a model system for testing the in vivo relevance of in vitro differential viral replication and cytopathicity, to identify the genetic determinants of HIV-1 pathogenesis in vivo and to screen the efficacy of envelope- based vaccines in protection from disease progression. The investigators propose to use both biologic and genetic approaches to: (1) establish the in vitro correlates of SHIV pathogenesis in vivo and 92) to generate a pathogenic SHIV33A clone for identification of sequence changes that correlate with changes in vitro biologic and serological properties and in vivo viral pathogenesis. As well, pathogenic envelope SHIV, which resembles more closely the properties of a primary HIV-1 isolate in terms of co-receptors usage and envelope antigenic structure, is proposed to be constructed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041945-02
Application #
2673121
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016
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Ho, Siu-hong; Shek, Lili; Gettie, Agegnehu et al. (2005) V3 loop-determined coreceptor preference dictates the dynamics of CD4+-T-cell loss in simian-human immunodeficiency virus-infected macaques. J Virol 79:12296-303
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Harouse, J M; Gettie, A; Eshetu, T et al. (2001) Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIV(SF162P3). J Virol 75:1990-5
Malenbaum, S E; Yang, D; Cheng-Mayer, C (2001) Evidence for similar recognition of the conserved neutralization epitopes of human immunodeficiency virus type 1 envelope gp120 in humans and macaques. J Virol 75:9287-96
Harouse, J M; Gettie, A; Tan, R C et al. (2001) Pathogenic determinants of the mucosally transmissible CXCR4-specific SHIV(SF33A2) map to env region. J Acquir Immune Defic Syndr 27:222-8

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