A new effort concentrating on animal models of AIDS was undertaken in August, 1987. Two model systems were established: (1) a primate model using the various simian immunodeficiency viruses (SIV); and (2) a feline model using the feline immunodeficiency virus (FIV). These viruses belong to the lentivirus subfamily of retroviruses and induce chronic persistent infection and immunodeficiency viruses (HIV-1 and HIV-2), while FIV is much less closely related to human or primate viruses based on lack of antigenic cross-reactivity and limited sequence homology. Challenge pools of FIV and several SIVs have been prepared and are undergoing infectivity titration in animals. Disease (simian AIDS) has been produced by SIV and cats have been infected by FIV, but to date minimal disease has been detected. Both FIVs and SIVs have been cloned and sequenced and their sequences compared with those of other related lentiviruses. Genetic drift of SIV over a 12 month interval was documented in monkeys experimentally infected with a molecular clone of SIVsm. Significant variation was detected in the envelope glycoprotein gene but not in the integrase gene. SIV isolates from healthy infected monkeys accumulated multiple in-frame stop codons in the env gene, whereas isolates from immunodeficient animals did not have such mutations. An inactivated SIV vaccine prepared by psoralen/UV treatment induced SIV envelope glycoprotein antibodies after a single inoculation. Significant sequence diversity in the env gene was detected among FIV isolates from different geographic locations. Also, serologic evidence of infection with FIV was detected with high frequency among free-ranging, wild caught felids such as Florida panthers (Felis concolor).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000370-07
Application #
3809638
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Sanders-Beer, Brigitte E; Eschricht, Magdalena; Seifried, Janna et al. (2012) Characterization of a monoclonal anti-capsid antibody that cross-reacts with three major primate lentivirus lineages. Virology 422:402-12
Kuwata, Takeo; Nishimura, Yoshiaki; Whitted, Sonya et al. (2009) Association of progressive CD4(+) T cell decline in SIV infection with the induction of autoreactive antibodies. PLoS Pathog 5:e1000372
Dang, Que; Goeken, Robert M; Brown, Charles R et al. (2008) Adaptive evolution of simian immunodeficiency viruses isolated from 2 conventional-progressor macaques with encephalitis. J Infect Dis 197:1695-700
Gautam, Rajeev; Carter, Anders Chase; Katz, Nathalia et al. (2007) In vitro characterization of primary SIVsmm isolates belonging to different lineages. In vitro growth on rhesus macaque cells is not predictive for in vivo replication in rhesus macaques. Virology 362:257-70
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
Brown, Charles R; Czapiga, Meggan; Kabat, Juraj et al. (2007) Unique pathology in simian immunodeficiency virus-infected rapid progressor macaques is consistent with a pathogenesis distinct from that of classical AIDS. J Virol 81:5594-606
Kuwata, Takeo; Byrum, Russell; Whitted, Sonya et al. (2007) A rapid progressor-specific variant clone of simian immunodeficiency virus replicates efficiently in vivo only in the absence of immune responses. J Virol 81:8891-904
Pandrea, Ivona; Apetrei, Cristian; Gordon, Shari et al. (2007) Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts. Blood 109:1069-76
Kuwata, Takeo; Dehghani, Houman; Brown, Charles R et al. (2006) Infectious molecular clones from a simian immunodeficiency virus-infected rapid-progressor (RP) macaque: evidence of differential selection of RP-specific envelope mutations in vitro and in vivo. J Virol 80:1463-75
Pandrea, Ivona; Silvestri, Guido; Onanga, Richard et al. (2006) Simian immunodeficiency viruses replication dynamics in African non-human primate hosts: common patterns and species-specific differences. J Med Primatol 35:194-201

Showing the most recent 10 out of 33 publications