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

• DOI: 10.1371/journal.ppat.1004467
• Publication Date: 2014-10-30T18:22:21Z
• Authors: Luca Micci; Xavier Alvarez; Robin I. Iriele; Alexandra M. Ortiz; Emily S. Ryan; Colleen S. McGary; Claire Deleage; Brigitte B. McAtee; Tianyu He; Cristian Apetrei; Kirk Easley; Savita Pahwa; Ronald G. Collman; Cynthia A. Derdeyn; Miles P. Davenport; Jacob D. Estes; Guido Silvestri; Andrew A. Lackner; Mirko Paiardini
• Keywords: Viremia; Simian immunodeficiency virus; Tissue tropism

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