1. A macaque model of HIV-1 infection
- Author
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Hatziioannou, Theodora, Ambrose, Zandrea, Chung, Nancy P.Y., Piatak, Michael, Jr., Yuan, Fang, Trubey, Charles M., Coalter, Vicky, Kiser, Rebecca, Schneider, Doug, Pung, Jeremy Smedleyd Rhonda, Gathuka, Mercy, Estes, Jacob D., Veazey, Ronald S., KewalRamani, Vineet N., Lifson, Jeffrey D., and Bieniasz, Paul D.
- Subjects
HTLV-I (Virus) -- Usage ,HTLV-I (Virus) -- Properties ,AIDS research -- Models ,AIDS (Disease) -- Research ,AIDS (Disease) -- Models ,Science and technology - Abstract
The lack of a primate model that utilizes HIV-1 as the challenge virus is an impediment to AIDS research; existing models generally employ simian viruses that are divergent from HIV-1, reducing their usefulness in preclinical investigations. Based on an understanding of species-specific variation in primate TRIM5 and APOBEC3 antiretroviral genes, we constructed simian-tropic (st)HIV-1 strains that differ from HIV-1 only in the vif gene. We demonstrate that such minimally modified stHIV-1 strains are capable of high levels of replication in vitro in pig-tailed macaque (Macaca nemestrina) lymphocytes. Importantly, infection of pig-tailed macaques with stHIV-1 results in acute viremia, approaching the levels observed in HIV-1-infected humans, and an ensuing persistent infection for several months, stHIV-1 replication was controlled thereafter, at least in part, by CD8+ T cells. We demonstrate the potential utility of this HIV-1-based animal model in a chemoprophylaxis experiment, by showing that a commonly used HIV-1 therapeutic regimen can provide apparently sterilizing protection from infection following a rigorous high-dose stHIV-1 challenge. AIDS | PrEP | SIV | stHIV-1
- Published
- 2009