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Journal of Virology, August 2009, p. 7517-7523, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00552-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Is the Gut the Major Source of Virus in Early Simian Immunodeficiency Virus Infection?

Matthew D. H. Lay,^1, Janka Petravic,¹ Shari N. Gordon,² Jessica Engram,² Guido Silvestri,^2,3 and Miles P. Davenport^1*

Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington NSW 2052, Australia,¹ Departments of Pathology and Laboratory Medicine and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,² Yerkes National Primate Research Center, Emory University, Atlanta, Georgia³

Received 18 March 2009/ Accepted 11 May 2009

The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4⁺ T cells from the guts of infected individuals. The large number of CD4⁺ T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4⁺ T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4⁺ T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4⁺ T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4⁺ T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4⁺ T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4⁺ T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection.

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* Corresponding author. Mailing address: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington NSW 2052, Australia. Phone: 61 2 9385 2762. Fax: 61 2 9385 1389. E-mail: m.davenport{at}unsw.edu.au

Published ahead of print on 20 May 2009.

Present address: Commonwealth Scientific and Industrial Research Organisation, Materials Science and Engineering, Clayton, VIC 3168, Australia.

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Journal of Virology, August 2009, p. 7517-7523, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00552-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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