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

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

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50 Scopus citations

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.

Original languageEnglish (US)
JournalPLoS pathogens
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2014

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Micci, L., Alvarez, X., Iriele, R. I., Ortiz, A. M., Ryan, E. S., McGary, C. S., Deleage, C., McAtee, B. B., He, T., Apetrei, C., Easley, K., Pahwa, S., Collman, R. G., Derdeyn, C. A., Davenport, M. P., Estes, J. D., Silvestri, G., Lackner, A. A., & 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). https://doi.org/10.1371/journal.ppat.1004467