title: A macaque model of HIV-1 infection.
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.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10021, USA. thatziio@adarc.org
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
authors.forename: Zandrea
authors.initials: Z
authors.lastname: Ambrose
authors.forename: Nancy P Y
authors.initials: NP
authors.lastname: Chung
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Charles M
authors.initials: CM
authors.lastname: Trubey
authors.forename: Vicky
authors.initials: V
authors.lastname: Coalter
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kiser
authors.forename: Doug
authors.initials: D
authors.lastname: Schneider
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.forename: Rhonda
authors.initials: R
authors.lastname: Pung
authors.forename: Mercy
authors.initials: M
authors.lastname: Gathuka
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.forename: Vineet N
authors.initials: VN
authors.lastname: KewalRamani
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018890:Chemoprevention; D004195:Disease Models, Animal; D005818:Genetic Engineering; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D008251:Macaca; D014766:Viremia; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents