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

Micci, L and Alvarez, X and Iriele, RI and Ortiz, AM and Ryan, ES and McGary, CS and Deleage, C and McAtee, BB and He, T and Apetrei, C and Easley, K and Pahwa, S and Collman, RG and Derdeyn, CA and Davenport, MP and Estes, JD and Silvestri, G and Lackner, AA and Paiardini, M (2014) CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells. PLoS Pathogens, 10 (10). ISSN 1553-7366

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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.

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Creators	Email	Pitt Username
Micci, L
Alvarez, X
Iriele, RI
Ortiz, AM
Ryan, ES
McGary, CS
Deleage, C
McAtee, BB
He, T	tih19@pitt.edu	TIH19
Apetrei, C	apetreic@pitt.edu	APETREIC
Easley, K
Pahwa, S
Collman, RG
Derdeyn, CA
Davenport, MP
Estes, JD
Silvestri, G
Lackner, AA
Paiardini, M