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Journal of Virology, August 2009, p. 7894-7908, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00444-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Simian Immunodeficiency Virus SIVrcm, a Unique CCR2-Tropic Virus, Selectively Depletes Memory CD4+ T Cells in Pigtailed Macaques through Expanded Coreceptor Usage In Vivo {triangledown}

Rajeev Gautam,1 Thaidra Gaufin,1 Isolde Butler,1 Aarti Gautam,1 Mary Barnes,1 Daniel Mandell,1 Melissa Pattison,1 Coty Tatum,1 Jeanne Macfarland,2 Christopher Monjure,1 Preston A. Marx,1,3 Ivona Pandrea,2,4 and Cristian Apetrei1,3*

Divisions of Microbiology,1 Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana 70433,2 Department of Tropical Medicine, School of Public Health and Tropical Medicine,3 Department of Pathology, School of Medicine, Tulane University, New Orleans, Louisiana 701124

Received 3 March 2009/ Accepted 29 May 2009

Simian immunodeficiency virus SIVrcm, which naturally infects red-capped mangabeys (RCMs), is the only SIV that uses CCR2 as its main coreceptor due to the high frequency of a CCR5 deletion in RCMs. We investigated the dynamics of SIVrcm infection to identify specific pathogenic mechanisms associated with this major difference in SIV biology. Four pigtailed macaques (PTMs) were infected with SIVrcm, and infection was monitored for over 2 years. The dynamics of in vivo SIVrcm replication in PTMs was similar to that of other pathogenic and nonpathogenic lymphotropic SIVs. Plasma viral loads (VLs) peaked at 107 to 109 SIVrcm RNA copies/ml by day 10 postinoculation (p.i.). A viral set point was established by day 42 p.i. at 103 to 105 SIVrcm RNA copies/ml and lasted up to day 180 p.i., when plasma VLs decreased below the threshold of detection, with blips of viral replication during the follow-up. Intestinal SIVrcm replication paralleled that of plasma VLs. Up to 80% of the CD4+ T cells were depleted by day 28 p.i. in the gut. The most significant depletion (>90%) involved memory CD4+ T cells. Partial CD4+ T-cell restoration was observed in the intestine at later time points. Effector memory CD4+ T cells were the least restored. SIVrcm strains isolated from acutely infected PTMs used CCR2 coreceptor, as reported, but expansion of coreceptor usage to CCR4 was also observed. Selective depletion of effector memory CD4+ T cells is in contrast with predicted in vitro tropism of SIVrcm for macrophages and is probably due to expansion of coreceptor usage. Taken together, these findings emphasize the importance of understanding the selective forces driving viral adaptation to a new host.

* Corresponding author. Mailing address: Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433. Phone: (985) 871-6518. Fax: (985) 871-6248. E-mail: capetrei{at}tulane.edu

{triangledown} Published ahead of print on 3 June 2009.

Journal of Virology, August 2009, p. 7894-7908, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00444-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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