Abstract

The overall goal of this proposal is to characterize and to optimize a new animal model utilizing a chimeric SIVmac/HIV-1 virus. The chimeric virus contains the long terminal repeats and intact gag, pro, pol, vif, vpx, vpr and nef genes of an infectious, pathogenic clone of SIVmac239 and the tat, rev, vpu and env genes of HIV-1. This chimeric virus, unlike HIV-1, replicates in macaque peripheral blood mononuclear cells and in cynomolgus monkeys. This virus should be useful for HIV-1 vaccine development. This revised study will focus on two specific aims: 1) To optimize the chimeric virus for persistence and pathogenicity in monkeys by in vivo passage as well as vpu and env gene modifications; and 2) to characterize the antiviral immune response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033832-02
Application #
2068889
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1993-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Cayabyab, Mark; Rohne, Daniela; Pollakis, Georgios et al. (2004) Rapid CD4+ T-lymphocyte depletion in rhesus monkeys infected with a simian-human immunodeficiency virus expressing the envelope glycoproteins of a primary dual-tropic Ethiopian Clade C HIV type 1 isolate. AIDS Res Hum Retroviruses 20:27-40
Song, Byeongwoon; Cayabyab, Mark; Phan, Ngoc et al. (2004) Neutralization sensitivity of a simian-human immunodeficiency virus (SHIV-HXBc2P 3.2N) isolated from an infected rhesus macaque with neurological disease. Virology 322:168-81
Etemad-Moghadam, B; Rhone, D; Steenbeke, T et al. (2001) Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. J Virol 75:5646-55
Liao, H X; Etemad-Moghadam, B; Montefiori, D C et al. (2000) Induction of antibodies in guinea pigs and rhesus monkeys against the human immunodeficiency virus type 1 envelope: neutralization of nonpathogenic and pathogenic primary isolate simian/human immunodeficiency virus strains. J Virol 74:254-63
LaBonte, J A; Patel, T; Hofmann, W et al. (2000) Importance of membrane fusion mediated by human immunodeficiency virus envelope glycoproteins for lysis of primary CD4-positive T cells. J Virol 74:10690-8
Reimann, K A; Watson, A; Dailey, P J et al. (1999) Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses. Virology 256:15-21
Etemad-Moghadam, B; Sun, Y; Nicholson, E K et al. (1999) Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo. J Virol 73:8873-9
Cayabyab, M; Karlsson, G B; Etemad-Moghadam, B A et al. (1999) Changes in human immunodeficiency virus type 1 envelope glycoproteins responsible for the pathogenicity of a multiply passaged simian-human immunodeficiency virus (SHIV-HXBc2). J Virol 73:976-84
Chen, Z W; Zhou, D; Chalifoux, L et al. (1997) Disseminated granulomatous disease in a simian immunodeficiency virus- and bacille Calmette-Guerin-infected rhesus monkey. AIDS 11:266-7
Li, A; Baba, T W; Sodroski, J et al. (1997) Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins. AIDS Res Hum Retroviruses 13:647-56

Showing the most recent 10 out of 21 publications