Low levels of SIV infection in sooty mangabey central memory CD4+ T cells are associated with limited CCR5 expression

M Paiardini, B Cervasi, E Reyes-Aviles, L Micci… - Nature medicine, 2011 - nature.com
M Paiardini, B Cervasi, E Reyes-Aviles, L Micci, AM Ortiz, A Chahroudi, C Vinton…
Nature medicine, 2011nature.com
Naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys do not progress to
AIDS despite high-level virus replication. We previously showed that the fraction of CD4+
CCR5+ T cells is lower in sooty mangabeys compared to humans and macaques. Here we
found that, after in vitro stimulation, sooty mangabey CD4+ T cells fail to upregulate CCR5
and that this phenomenon is more pronounced in CD4+ central memory T cells (TCM cells).
CD4+ T cell activation was similarly uncoupled from CCR5 expression in sooty mangabeys …
Abstract
Naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4+CCR5+ T cells is lower in sooty mangabeys compared to humans and macaques. Here we found that, after in vitro stimulation, sooty mangabey CD4+ T cells fail to upregulate CCR5 and that this phenomenon is more pronounced in CD4+ central memory T cells (TCM cells). CD4+ T cell activation was similarly uncoupled from CCR5 expression in sooty mangabeys in vivo during acute SIV infection and the homeostatic proliferation that follows antibody-mediated CD4+ T cell depletion. Sooty mangabey CD4+ TCM cells that express low amounts of CCR5 showed reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4+ TCM cells of rhesus macaques. These data suggest that low CCR5 expression on sooty mangabey CD4+ T cells favors the preservation of CD4+ T cell homeostasis and promotes an AIDS-free status by protecting CD4+ TCM cells from direct virus infection.
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