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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

© 2014. 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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Micci, L
Alvarez, X
Iriele, RI
Ortiz, AM
Ryan, ES
McGary, CS
Deleage, C
McAtee, BB
He, Ttih19@pitt.eduTIH19
Apetrei, Capetreic@pitt.eduAPETREIC
Easley, K
Pahwa, S
Collman, RG
Derdeyn, CA
Davenport, MP
Estes, JD
Silvestri, G
Lackner, AA
Paiardini, M
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorDouek, Daniel CUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 10
Number: 10
DOI or Unique Handle: 10.1371/journal.ppat.1004467
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
ISSN: 1553-7366
Other ID: NLM PMC4214815
PubMed Central ID: PMC4214815
PubMed ID: 25356757
Date Deposited: 12 May 2015 18:49
Last Modified: 02 Feb 2019 13:58
URI: http://d-scholarship.pitt.edu/id/eprint/24039

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