Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection

Abstract

It has recently been established that both acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are accompanied by a dramatic and selective loss of memory CD4+ T cells predominantly from the mucosal surfaces. The mechanism underlying this depletion of memory CD4+ T cells (that is, T-helper cells specific to previously encountered pathogens) has not been defined. Using highly sensitive, quantitative polymerase chain reaction together with precise sorting of different subsets of CD4+ T cells in various tissues, we show that this loss is explained by a massive infection of memory CD4+ T cells by the virus. Specifically, 30–60% of CD4+ memory T cells throughout the body are infected by SIV at the peak of infection, and most of these infected cells disappear within four days. Furthermore, our data demonstrate that the depletion of memory CD4+ T cells occurs to a similar extent in all tissues. As a consequence, over one-half of all memory CD4+ T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase—an insult that certainly heralds subsequent immunodeficiency. Our findings point to the importance of reducing the cell-associated viral load during acute infection through therapeutic or vaccination strategies.

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Figure 1: Identification of subsets of CD4+ and CD8+ T cells in a non-human primate (rhesus macaque).
Figure 2: Dynamics of CD4+ and CD8+ subsets during acute SIV infection.
Figure 3: Viral dynamics during acute infection.
Figure 4: Expression of CCR5 mRNA by T cells.

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Acknowledgements

We thank R. Koup for critical comments on the manuscript; S. Perfetto, J. Yu, R. Nguyen, D. Ambrozak and other members of the VRC Laboratory of Immunology for advice and technical help; M. St Claire for assistance with the animals; and S. Rao, V. Dang and J.-P. Todd for their assistance during the course of this study.

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Correspondence to Mario Roederer.

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Mattapallil, J., Douek, D., Hill, B. et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097 (2005). https://doi.org/10.1038/nature03501

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