title: CD4 depletion in SIV-infected macaques results in macrophage and microglia infection with rapid turnover of infected cells.
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.
authors.affiliation: Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Luca
authors.initials: L
authors.lastname: Micci
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.affiliation: Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Robin I
authors.initials: RI
authors.lastname: Iriele
authors.affiliation: Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Ryan
authors.affiliation: Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: McGary
authors.affiliation: AIDS Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, Maryland, United States of America.
authors.forename: Claire
authors.initials: C
authors.lastname: Deleage
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
authors.forename: Brigitte B
authors.initials: BB
authors.lastname: McAtee
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Tianyu
authors.initials: T
authors.lastname: He
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.affiliation: Department of Biostatistics & Bioinformatics, Rollins School of Public Health, Atlanta, Georgia, United States of America.
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.affiliation: University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Collman
authors.affiliation: 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.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.affiliation: Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia.
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
authors.affiliation: AIDS Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, Maryland, United States of America.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: 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.
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.affiliation: 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.
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000821:virology; D017628:Microglia / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load; D014766:Viremia