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

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. © 2014.