A new study from Miles Davenport and colleagues, just published online in the Journal of Virology, uses repeated sampling of SIV-infected monkeys to show that, in the majority of cases, gut CD4 T cell loss happens so quickly that these cells cannot contribute substantially to the high levels of viral load that occur during acute SIV infection. The authors note that prior studies did not sample animals with sufficient frequency to detect that loss of gut CD4 T cells typically precedes peak viral load by 4-5 days. In contrast, the researchers observed that peak CD4 T cell loss from lymphoid tissues, bronchoalveolar lavage (BaL) and peripheral blood coincided with peak viral load.
JVI Accepts, published online ahead of print on 20 May 2009
J. Virol. doi:10.1128/JVI.00552-09
Is gut the major source of virus in early SIV infection?
Matthew D. H. Lay, Janka Petravic, Shari N. Gordon, Jessica Engram, Guido Silvestri, and Miles P Davenport*
Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington NSW 2052, Australia; Departments of Pathology & Laboratory Medicine, and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA
The acute phases of HIV and SIV infection are characterized by rapid and profound depletion of CD4+ T cells from the gut of infected individuals. The large number of CD4+ T cells in the gut (a large fraction of which is activated and expresses the HIV/SIV co-receptor 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 use data on CD4+ T cell proportions in the lamina propria of the rectum of SIV infected rhesus macaques (that progress to AIDS) and sooty mangabeys (that 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. By contrast, the maximum loss rate of CD4+ T cells from broncho-alveolar lavage and lymph node 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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