Investigations of HIV-1 pathogenesis have also been hampered by a lack of a tractable animal model: with the exception of one recent report, HIV-1 inoculations of chimpanzees do not result in immunodeficiency. When it became clear that SIV, the close primate lentivirus relative of HIV-1, induced an immunodeficiency in Asian macaques with clinical features similar to AIDS in man, SIV/HIV chimeric viruses (SHIVs) were constructed to address pathogenicity and vaccine issues related to the incorporated HIV- 1 sequences. Compared to SIV, however, many of the first- generation SHIVs did not replicate to high levels in vivo or induce disease. During the past year a pathogenic SHIV virus containing the HIV-1 tat, rev, vpu and env genes was constructed. This virus was used to challenge macaques previously immunized with a live attenuated SIV vaccine. Despite having dissimilar Env glycoproteins and, in the absence of detectable neutralizing antibodies, the vaccinated macaques were protected from a subsequent infection with a SHIV virus. In a separate group of experiments, the role of CD8 T lymphocytes in resolving primary lentiviral infections was studies by administering mouse-anti- human CD8 monoclonal antibodies (mAb) at the time of the acute SHIV infection. Animals treated with such antibody failed to clear the virus promptly, exhibited 100-fold higher peak virus load, and sustained greater depletion of CD4 T lymphocytes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000415-14
Application #
6098932
Study Section
Special Emphasis Panel (LMM)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Nishimura, Yoshiaki; Sadjadpour, Reza; Mattapallil, Joseph J et al. (2009) High frequencies of resting CD4+ T cells containing integrated viral DNA are found in rhesus macaques during acute lentivirus infections. Proc Natl Acad Sci U S A 106:8015-20
Nishimura, Yoshiaki; Igarashi, Tatsuhiko; Buckler-White, Alicia et al. (2007) Loss of naive cells accompanies memory CD4+ T-cell depletion during long-term progression to AIDS in Simian immunodeficiency virus-infected macaques. J Virol 81:893-902
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Igarashi, Tatsuhiko; Imamichi, Hiromi; Brown, Charles R et al. (2003) The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4+ T cell-depleted rhesus monkeys. J Leukoc Biol 74:772-80
Lafont, Bernard A P; Buckler-White, Alicia; Plishka, Ron et al. (2003) Characterization of pig-tailed macaque classical MHC class I genes: implications for MHC evolution and antigen presentation in macaques. J Immunol 171:875-85
Igarashi, Tatsuhiko; Donau, Olivia K; Imamichi, Hiromi et al. (2003) Macrophage-tropic simian/human immunodeficiency virus chimeras use CXCR4, not CCR5, for infections of rhesus macaque peripheral blood mononuclear cells and alveolar macrophages. J Virol 77:13042-52

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