Simian immunodeficiency virus SIVagm dynamics in African green monkeys.
The mechanisms underlying the lack of disease progression in natural simian immunodeficiency virus (SIV) hosts are still poorly understood. To test the hypothesis that SIV-infected African green monkeys (AGMs) avoid AIDS due to virus replication occurring in long-lived infected cells, we infected six animals with SIVagm and treated them with potent antiretroviral therapy [ART; 9-R-(2-phosphonomethoxypropyl) adenine (tenofovir) and beta-2,3-dideoxy-3-thia-5-fluorocytidine (emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 h after ART initiation. A significant decrease of viral load was observed in peripheral blood mononuclear cells and intestine. Mathematical modeling of viremia decay post-ART indicates a half-life of productively infected cells ranging from 4 to 9.5 h, i.e., faster than previously reported for human immunodeficiency virus and SIV. ART induced a slight but significant increase in peripheral CD4(+) T-cell counts but no significant changes in CD4(+) T-cell levels in lymph nodes and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation, and apoptosis, already low in AGMs chronically infected with SIVagm. Collectively, these results indicate that, in SIVagm-infected AGMs, the bulk of virus replication is sustained by short-lived cells; therefore, differences in disease outcome between SIVmac infection of macaques and SIVagm infection of AGMs are unlikely due to intrinsic differences in the in vivo cytopathicities between the two viruses.
Pandrea
Ivona
I
Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA. ipandrea@tulane.edu
Ribeiro
Ruy M
RM
Gautam
Rajeev
R
Gaufin
Thaidra
T
Pattison
Melissa
M
Barnes
Mary
M
Monjure
Christopher
C
Stoulig
Crystal
C
Dufour
Jason
J
Cyprian
Wayne
W
Silvestri
Guido
G
Miller
Michael D
MD
Perelson
Alan S
AS
Apetrei
Cristian
C
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002522:Chlorocebus aethiops / Q000821:virology*; D007422:Intestines / Q000276:immunology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology; D008962:Models, Theoretical; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D019562:Viral Load; D014766:Viremia
D019380:Anti-HIV Agents