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 Estes, Ronald S. Veazey, Vineet N. Kewalramani, Jeffrey D. Lifson, Paul D. Bieniasz

Research output: Contribution to journalArticle

105 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Macaca
HIV Infections
HIV-1
Primates
Swine
Infection
Macaca nemestrina
vif Genes
Viruses
Viremia
Chemoprevention
Acquired Immunodeficiency Syndrome
Animal Models
HIV
Lymphocytes
T-Lymphocytes
Research
Genes

Keywords

  • AIDS
  • PrEP
  • SIV
  • StHIV-1

ASJC Scopus subject areas

  • General

Cite this

Hatziioannou, T., Ambrose, Z., Chung, N. P. Y., Piatak, M., Yuan, F., Trubey, C. M., ... 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

A macaque model of HIV-1 infection. / Hatziioannou, Theodora; Ambrose, Zandrea; Chung, Nancy P Y; Piatak, Michael; Yuan, Fang; Trubey, Charles M.; Coalter, Vicky; Kiser, Rebecca; Schneider, Doug; Smedley, Jeremy; Pung, Rhonda; Gathuka, Mercy; Estes, Jacob; Veazey, Ronald S.; Kewalramani, Vineet N.; Lifson, Jeffrey D.; Bieniasz, Paul D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 11, 17.03.2009, p. 4425-4429.

Research output: Contribution to journalArticle

Hatziioannou, T, Ambrose, Z, Chung, NPY, Piatak, M, Yuan, F, Trubey, CM, Coalter, V, Kiser, R, Schneider, D, Smedley, J, Pung, R, Gathuka, M, Estes, J, Veazey, RS, Kewalramani, VN, Lifson, JD & Bieniasz, PD 2009, 'A macaque model of HIV-1 infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 11, pp. 4425-4429. https://doi.org/10.1073/pnas.0812587106
Hatziioannou T, Ambrose Z, Chung NPY, Piatak M, Yuan F, Trubey CM et al. A macaque model of HIV-1 infection. Proceedings of the National Academy of Sciences of the United States of America. 2009 Mar 17;106(11):4425-4429. https://doi.org/10.1073/pnas.0812587106
Hatziioannou, Theodora ; Ambrose, Zandrea ; Chung, Nancy P Y ; Piatak, Michael ; Yuan, Fang ; Trubey, Charles M. ; Coalter, Vicky ; Kiser, Rebecca ; Schneider, Doug ; Smedley, Jeremy ; Pung, Rhonda ; Gathuka, Mercy ; Estes, Jacob ; Veazey, Ronald S. ; Kewalramani, Vineet N. ; Lifson, Jeffrey D. ; Bieniasz, Paul D. / A macaque model of HIV-1 infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 11. pp. 4425-4429.
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