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


CD4+ T-cells are both mediators of antiviral immune response and critical targets for HIV replication. We have previously shown that experimental depletion of CD4+ T-cells prior to SIV infection in rhesus macaques results in higher viremia and the emergence of CD4-independent SIV-envelopes. The findings reported in this new study of CD4 depletion address key unanswered questions about the phenotype, location, and lifespan of the sources of the increased viral replication in the absence of CD4+ T-cells. Altogether, our new data indicate that depletion of CD4+ T-cells prior to SIV infection results in activation of monocyte and massive infection of tissue-resident macrophages, which appear to be the predominant population of productively infected cells. Furthermore, our analysis of the slope of viremia decline after initiation of antiretroviral therapy suggests that the lifespan of these virus targets is markedly shorter than those previously estimated for macrophages. In summary, in the context of CD4+ T-cell depletion macrophages can be highly infectable, exhibit rapid turnover, and short in vivo lifespan. These finding raises a suggestive hypothesis that eradication of HIV from this reservoir could be enhanced by therapeutics able to modulate monocyte/macrophage turnover.


Vyšlo v časopise: CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004467
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004467

Souhrn

CD4+ T-cells are both mediators of antiviral immune response and critical targets for HIV replication. We have previously shown that experimental depletion of CD4+ T-cells prior to SIV infection in rhesus macaques results in higher viremia and the emergence of CD4-independent SIV-envelopes. The findings reported in this new study of CD4 depletion address key unanswered questions about the phenotype, location, and lifespan of the sources of the increased viral replication in the absence of CD4+ T-cells. Altogether, our new data indicate that depletion of CD4+ T-cells prior to SIV infection results in activation of monocyte and massive infection of tissue-resident macrophages, which appear to be the predominant population of productively infected cells. Furthermore, our analysis of the slope of viremia decline after initiation of antiretroviral therapy suggests that the lifespan of these virus targets is markedly shorter than those previously estimated for macrophages. In summary, in the context of CD4+ T-cell depletion macrophages can be highly infectable, exhibit rapid turnover, and short in vivo lifespan. These finding raises a suggestive hypothesis that eradication of HIV from this reservoir could be enhanced by therapeutics able to modulate monocyte/macrophage turnover.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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