A macaque model of HIV-1 infection

Theodora Hatziioannou, Zandrea Ambrose, Nancy P.Y. Chung, Michael Piatak, Fang Yuan, Charles M. Trubey, Vicky Coalter, Rebecca Kiser, Doug Schneider, Jeremy Smedley, Rhonda Pung, Mercy Gathuka, Jacob D. Estes, Ronald S. Veazey, Vineet N. Kewalramani, Jeffrey D. Lifson, Paul D. Bieniasz

Research output: Contribution to journalArticle

108 Scopus citations

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 anti- retroviral genes, we constructed simian-tropic (st)HIV-l 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.

Original languageEnglish (US)
Pages (from-to)4425-4429
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number11
DOIs
StatePublished - Mar 17 2009

Keywords

  • AIDS
  • PrEP
  • SIV
  • StHIV-1

ASJC Scopus subject areas

  • General

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    Hatziioannou, T., Ambrose, Z., Chung, N. P. Y., Piatak, M., Yuan, F., Trubey, C. M., Coalter, V., Kiser, R., Schneider, D., Smedley, J., Pung, R., Gathuka, M., Estes, J. D., Veazey, R. S., Kewalramani, V. N., Lifson, J. D., & Bieniasz, P. D. (2009). A macaque model of HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America, 106(11), 4425-4429. https://doi.org/10.1073/pnas.0812587106