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

• Authors: Mirko Paiardini, Emory University; Barbara Cervasi, Emory University; Elane Reyes-Aviles, Case Western University; Luca Micci, Emory University; Alexandra M. Ortiz, Emory University; Ann Chahroudi, Emory University; Carol Vinton, National Institutes of Health; Shari N. Gordon, National Institutes of Health; Steven Bosinger, Emory University; Nicholas Francella, University of Pennsylvania; Paul L. Hallberg, University of Pennsylvania; Timothy Schlub, University of New South Wales; Ming Liang Chan, University of New South Wales; Nadeene E. Riddick, University of Pennsylvania; Ronald G. Collman, University of Pennsylvania; Cristian Apetrei, University of Pittsburgh; Ivona Pandrea, University of Pittsburgh; James Else, Emory University; Jan Munch, University Hospital Ulm; Frank Kirchhoff, University Hospital Ulm; Miles P. Davenport, University of New South Wales; Guido Silvestri, Emory University
• Journal Title: Nature Medicine
• Volume: Volume 17, Number 7
• Publisher: Nature Publishing Group | 2011-06-26, Pages 830-836
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/nm.2395
• Subjects: Health Sciences, Medicine and Surgery

Abstract

Naturally SIV-infected sooty mangabeys (SMs) do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4+CCR5+ T-cells is lower in SMs compared to humans and macaques. Here we found that, after in vitro stimulation, SM CD4+ T-cells fail to up-regulate CCR5, and that this phenomenon is more pronounced in CD4+ central-memory T-cells (TCM). CD4+ T-cell activation was similarly uncoupled from CCR5 expression in SMs in vivo during (i) acute SIV infection and (ii) following antibody-mediated CD4+ T-cell depletion. Remarkably, CD4+ TCM of SMs that express low levels of CCR5 demonstrated reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4+ TCM of RMs. These data suggest that low CCR5 expression on SM CD4+ T-cells favors the preservation of CD4+ T-cell homeostasis and promotes an AIDS-free status by protecting CD4+ TCM from direct virus infection.