Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques

• Type of Material: Article
• Authors: Nichole R. Klatt, National Institutes of Health; Lauren A. Canary, National Institutes of Health; Thomas Vanderford, Emory University; Carol L. Vinton, National Institutes of Health; Jessica C. Engram, Emory University; Richard M. Dunham, Emory University; Heather E. Cronise, National Institutes of Health; Joanna M. Swerczek, National Institutes of Health; Bernard A. P. Lafont, National Institutes of Health; Louis J. Picker, Oregon Health & Science University; Guido Silvestri, Emory University; Jason M. Brenchley, National Institutes of Health
• Language: English
• Date: 2012-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2012, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.06033-11
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 86
• Issue: 2
• Start Page: 1203
• End Page: 1213
• Grant/Funding Information: These studies were supported by the intramural program of the National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, and in part by NIH grants R01-AI90797; to G. Silvestri and AI054292 to L. Picker as well as ONPRC Core grant RR00163.
• Keywords: ACUTE SIV INFECTION; Virology; AFRICAN INDIVIDUALS; MACACA-NEMESTRINA; Science & Technology; PIG-TAILED MACAQUES; IN-VIVO; HIV-1 INFECTION; IMMUNE ACTIVATION; MOLECULAR CLONES; CD4(+) T-CELLS; VIROLOGY; Life Sciences & Biomedicine; TYPE-1 INFECTION
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Microbiology

Abstract

Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P=0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P=0.7953 and P=0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4 + T cell depletion, as CD4 + T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.