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Journal of Virology, December 2007, p. 13865-13875, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.00452-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CD4⁺ CCR5⁺ T-Cell Dynamics during Simian Immunodeficiency Virus Infection of Chinese Rhesus Macaques ^,

V. Monceaux,¹ L. Viollet,¹ F. Petit,¹ M. C. Cumont,¹ G. R. Kaufmann,² A. M. Aubertin,³ B. Hurtrel,¹ G. Silvestri,⁴ and J. Estaquier^1,5,6*

Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France,¹ Division of Infectious Diseases and Hospital Epidemiology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland,² INSERM U74, Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France,³ Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,⁴ INSERM U841, 94014 Créteil, France,⁵ Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France⁶

Received 2 March 2007/ Accepted 12 September 2007

Simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) provides a reliable model to study the relationship between lentivirus replication, cellular immune responses, and CD4⁺ T-cell dynamics. Here we investigated, using SIVmac251-infected RMs of a Chinese genetic background (which experience a slower disease progression than Indian RMs), the dynamics of CD4⁺ CCR5⁺ T cells, as this subset of memory/activated CD4⁺ T cells is both a preferential target of virus replication and a marker of immune activation. As expected, we observed that the number of circulating CD4⁺ CCR5⁺ T cells decreases transiently at the time of peak viremia. However, at 60 days postinfection, i.e., when set-point viremia is established, the level of CD4⁺ CCR5⁺ T cells was increased compared to the baseline level. Interestingly, this increase correlated with faster disease progression, higher plasma viremia, and early loss of CD4⁺ T-cell function, as measured by CD4⁺ T-cell count, the fraction of memory CD4⁺ T cells, and the recall response to purified protein derivative. Taken together, these data show a key difference between the dynamics of the CD4⁺ CCR5⁺ T-cell pool (and its relationship with disease progression) in Chinese RMs and those described in previous reports for Indian SIVmac251-infected RMs. As the SIV-associated changes in the CD4⁺ CCR5⁺ T-cell pool reflect the opposing forces of SIV replication (which reduces this cellular pool) and immune activation (which increases it), our data suggest that in SIV-infected Chinese RMs the impact of immune activation is more prominent than that of virus replication in determining the size of the pool of CD4⁺ CCR5⁺ T cells in the periphery. As progression of HIV infection in humans also is associated with a relative expansion of the level of CD4⁺ CCR5⁺ T cells, we propose that SIV infection of Chinese RMs is a very valuable and important animal model for understanding the pathogenesis of human immunodeficiency virus infection.

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* Corresponding author. Mailing address: INSERM U841, Faculté Henri Mondor, 8 rue du Général Sarrail, 94010 Créteil, France. Phone: 33 1 49 81 36 72. Fax: 33 1 49 81 37 19. E-mail: estaquier{at}yahoo.fr

Published ahead of print on 26 September 2007.

This work is dedicated to the memory of B. Hurtel.

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Journal of Virology, December 2007, p. 13865-13875, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.00452-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.