Background
Although antiretroviral therapy (ART) effectively improves the life expectancy among people living with HIV (PLWH), persistent chronic immune activation and inflammation remain a concern. Recent studies suggest that some miRNA species in extracellular vesicles (EVs) play a role in modulating inflammation. We thus hypothesized that dysregulation of EVs’ miRNAs during HIV infection may be associated with HIV-related inflammation.
Methods
We isolated EVs from plasma samples comprising 16 untreated and 12 treated HIV-infected patients and 10 healthy individuals in Tanzania, and the total RNA within the resultant EVs was isolated. The relative abundance of 20 immunomodulatory miRNAs was quantified using RT-qPCR and assessed for association with the serum levels of IL-6, IL-10, sCD14, CRP, baseline CD4+ T cell count, and viral load.
Results
We observed a significant decrease in expression levels of six miRNAs, including miR-16-5p, 20a-5p, 142-3p, 146a-5p, 382-5p, and 615-5p (>9-fold, p<0.05) in the HIV-untreated group compared to the healthy control group. Compared to the untreated group, four of the six miRNAs (miR-16-5p, 20a-5p, 146a-3p, and 615-5p) showed a marked increase in the treated group but remained below healthy levels (p< 0.05), whereas the remaining two (miR-142-3p and 382-5p) showed no restoration. In contrast, expression levels of the remaining 14 miRNAs showed no substantial difference between the groups. Moreover, the expression levels of miR-16-5p and 615-5p significantly correlated inversely with sCD14 and IL-6 (p<0.05) in the treated group, suggesting a potential link between the dysregulated miRNAs in EVs and inflammation. None of the analyzed miRNAs was associated with plasma viral load, baseline CD4+ T cell count, CRP, or IL-10.
Conclusions
Collectively, we identified six miRNAs showing substantial dysregulation in EVs in HIV infection. In particular, expression levels of miR-16-5p and miR-615-5p in EVs correlated with inflammation markers in the treated group. These results suggest the potential usefulness of miR-16-5p and miR-615-5p as surrogate markers of chronic inflammation during antiviral treatment in PLWH.
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