Abstract

To create an animal model system in which the infecting virus more closely resembles HIV-1, chimeric viruses containing genetic elements of HIV-1 (tat, rev, vpu, env) in a background of SIVmac were constructed. Unlike HIV-1, these chimeric simian-human immunodeficiency viruses (SHIV) infect a variety of monkey species and elicit cellular and humoral immune responses similar to those observed in HIV-1 infected humans. An animal-passaged SHIV variant containing the envelope glycoproteins of a primary patient HIV-1 isolate can deplete CD4+ lymphocytes in rhesus monkeys in a rapid and specific fashion. In this competing renewal application, Dr. Sodroski proposes the following Specific Aims:
Specific Aim 1 : To obtain and characterize the pathogenic molecular clone SHIV.
Specific Aim 2 : To characterize viral and host variables that affect in vivo SHIV replication and pathogenicity.
Specific Aim 3 : To construct and assess in vivo additional SHIVs with env and pol replacements. SHIV chimerics with diverse envelop glycoproteins from primary HIV-1 isolates as well as SHIV constructs containing the reverse transcriptase of HIV 1 will be studied.
Specific Aim 4 : To examine the role of HIV-1 specific Vpu protein in SHIV replication and pathogenicity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033832-05
Application #
2390366
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1993-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
5
Fiscal Year
1997
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
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
Karlsson, G B; Halloran, M; Li, J et al. (1997) Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol 71:4218-25

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