Pathogenesis Studies of Simian Immunodeficiency Virus Infection of Macaques

Hirsch, Vanessa

Abstract

A crucial element in the development of effective therapeutic and prophylactic strategies for AIDS is an experimental animal model in which the course of immunodeficiency virus infection parallels the pathogenesis of the human disease. Simian immunodeficiency virus (SIV) infection of macaques satisfies this criterion and is therefore a relevant model. Notably, SIV induces an immunodeficiency syndrome in infected macaques that is remarkably similar in pathogenesis to human AIDS. An important use of this animal model system is the detailed study of pathogenesis and viral determinants of disease since many studies of this type are not feasible in humans. Such investigations should allow us to determine how primate lentiviruses destroy the immune system of their hosts, and this understanding should facilitate the development of more rational therapeutic antiviral strategies. The goals of this project include: 1) the molecular characterization of novel SIV's for phylogenetic studies and as reagents for pathogenesis and vaccine studies; and 2) delineation of the pathogenesis of SIV-induced AIDS.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000370-16
• Application #: 6098926
• Study Section: Special Emphasis Panel (LMM)
• Support Year: 16
• Fiscal Year: 1998

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

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

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

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

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