Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals

English version

Autoři: Elizabeth R. Wonderlich ^aff001; Krupa Subramanian ^aff001; Bryan Cox ^aff002; Ann Wiegand ^aff003; Carol Lackman-Smith ^aff001; Michael J. Bale ^aff003; Mars Stone ^aff004; Rebecca Hoh ^aff006; Mary F. Kearney ^aff003; Frank Maldarelli ^aff003; Steven G. Deeks ^aff006; Michael P. Busch ^aff004; Roger G. Ptak ^aff001; Deanna A. Kulpa ^aff002
Působiště autorů: Southern Research, Frederick, Maryland, United States of America ^aff001; Department of Pediatrics, Emory University, Atlanta, Georgia, United States of America ^aff002; HIV DRP, NCI at Frederick, NIH, Frederick, Maryland, United States of America ^aff003; Vitalant Research Institute, San Francisco, California, United States of America ^aff004; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, United States of America ^aff005; University of California, San Francisco (UCSF), San Francisco, California, United States of America ^aff006
Vyšlo v časopise: Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008074
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008074

Souhrn

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells.

Klíčová slova:

Cell differentiation – Cytokines – HIV-1 – Memory T cells – T cells – Viral persistence and latency – Viral replication

Zdroje

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