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Article
Nature 434, 1093-1097 (28 April 2005) | doi:10.1038/nature03501; Received 22 December 2004; Accepted 25 February 2005; Published online 27 March 2005
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Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection
Joseph J. Mattapallil1, Daniel C. Douek2, Brenna Hill2, Yoshiaki Nishimura3, Malcolm Martin3 & Mario Roederer1
- ImmunoTechnology Section and
- Human Immunology Section, Vaccine Research Center, and
- Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland 20892, USA
Correspondence to: Mario Roederer1 Correspondence and requests for materials should be addressed to M.R. (Email: Roederer@nih.gov).
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.
- ImmunoTechnology Section and
- Human Immunology Section, Vaccine Research Center, and
- Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, Maryland 20892, USA
Correspondence to: Mario Roederer1 Correspondence and requests for materials should be addressed to M.R. (Email: Roederer@nih.gov).
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