A macaque model of HIV-1 infection.
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.
Hatziioannou
Theodora
T
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10021, USA. thatziio@adarc.org
Ambrose
Zandrea
Z
Chung
Nancy P Y
NP
Piatak
Michael
M
Yuan
Fang
F
Trubey
Charles M
CM
Coalter
Vicky
V
Kiser
Rebecca
R
Schneider
Doug
D
Smedley
Jeremy
J
Pung
Rhonda
R
Gathuka
Mercy
M
Estes
Jacob D
JD
Veazey
Ronald S
RS
KewalRamani
Vineet N
VN
Lifson
Jeffrey D
JD
Bieniasz
Paul D
PD
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
D019380:Anti-HIV Agents