CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells

PLoS Pathogens

Claire Deleage¹  Guido Silvestri¹  Cristian Apetrei²  Tianyu He²  Jacob D. Estes³  Kirk Easley⁴  Ronald G. Collman⁵  Mirko Paiardini⁶  Miles P. Davenport⁶  Colleen S. McGary⁷  Alexandra M. Ortiz⁷  Emily S. Ryan⁷  Robin I. Iriele⁷  Luca Micci⁷  Andrew A. Lackner⁷  Cynthia A. Derdeyn⁸  Xavier Alvarez⁹  Brigitte B. McAtee⁹  Savita Pahwa^1,10 

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

关键词: T cells;    SIV;    Macrophages;    Monocytes;    Viral load;    Viremia;    Cloning;    Microglial cells;   

DOI  :  10.1371/journal.ppat.1004467

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY