Immune Cells Release MicroRNA-155 Enriched Extracellular Vesicles That Promote HIV-1 Infection

The hallmark of HIV-1 infection is the rapid dysregulation of immune functions. Recent investigations for biomarkers of such dysregulation in people living with HIV (PLWH) reveal a strong correlation between viral rebound and immune activation with an increased abundance of extracellular vesicles (EVs) enriched with microRNA-155. We propose that the activation of peripheral blood mononuclear cells (PBMCs) leads to an increased miR-155 expression and production of miR-155-rich extracellular vesicles (miR-155-rich EVs), which can exacerbate HIV-1 infection by promoting viral replication. PBMCs were incubated with either HIV-1 (NL4.3Balenv), a TLR-7/8 agonist, or TNF. EVs were harvested from the cell culture supernatant by differential centrifugation, and RT-qPCR quantified miR-155 in cells and derived EVs. The effect of miR-155-rich EVs on replication of HIV-1 in incubated PBMCs was then measured by viral RNA and DNA quantification. HIV-1, TLR7/8 agonist, and TNF each induced the release of miR-155-rich EVs by PBMCs. These miR-155-rich EVs increased viral replication in PBMCs infected in vitro. Infection with HIV-1 and inflammation promote the production of miR-155-rich EVs, enhancing viral replication. Such autocrine loops, therefore, could influence the course of HIV-1 infection by promoting viral replication.

Automated summary

The dysregulation of immune functions is a key characteristic of HIV-1 infection. Recent studies have found a strong correlation between viral rebound and immune activation in people living with HIV (PLWH), with an increased presence of microRNA-155 enriched extracellular vesicles (EVs). The activation of peripheral blood mononuclear cells (PBMCs) leads to the production of miR-155-rich EVs, which can exacerbate HIV-1 infection by promoting viral replication. In vitro experiments showed that these miR-155-rich EVs increased viral replication in PBMCs infected with HIV-1. These findings suggest that the production of miR-155-rich EVs in response to HIV-1 infection and inflammation can impact the course of the infection by enhancing viral replication.