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PLoS Pathog. 2014 Oct 30;10(10):e1004467. doi: 10.1371/journal.ppat.1004467. eCollection 2014 Oct.

CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.

Author information

1
Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
2
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
3
AIDS Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, Maryland, United States of America.
4
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
5
Department of Biostatistics & Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, United States of America.
6
University of Miami Miller School of Medicine, Miami, Florida, United States of America.
7
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
8
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
9
Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia.
10
Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.

Abstract

In rhesus macaques (RMs), experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i) set-point viral load two-logs higher than controls; (ii) macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii) substantial expansion of pro-inflammatory monocytes; (iv) aberrant activation and infection of microglial cells; and (v) lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.

PMID:
25356757
PMCID:
PMC4214815
DOI:
10.1371/journal.ppat.1004467
[Indexed for MEDLINE]
Free PMC Article
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