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Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4425-9. doi: 10.1073/pnas.0812587106. Epub 2009 Mar 2.

A macaque model of HIV-1 infection.

Author information

  • 1Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10021, USA. thatziio@adarc.org

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.

PMID:
19255423
[PubMed - indexed for MEDLINE]
PMCID:
PMC2657417
Free PMC Article

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