Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.
Elizabeth R WonderlichKrupa SubramanianBryan CoxAnn WiegandCarol Lackman-SmithMichael J BaleMars StoneRebecca HohMary F KearneyFrank MaldarelliSteven G DeeksMichael P BuschRoger G PtakDeanna A KulpaPublished in: PLoS pathogens (2019)
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.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- hiv testing
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- south africa
- heart rate
- regulatory t cells
- physical activity
- sars cov
- dendritic cells
- heart rate variability
- working memory
- blood pressure
- cell death
- oxidative stress
- endothelial cells
- cell proliferation
- single cell
- peripheral blood
- diabetic rats
- quantum dots
- helicobacter pylori infection