Type I Interferon Reprograms Intestinal Epithelial Cells for Sustained HIV-1 Latency in CD4+ T Cells of People with HIV-1 Receiving Antiretroviral Therapy

The intestinal environment sustains a state of HIV latency via yet unclear mechanisms. We recently demonstrated that specific cytokines act on intestinal epithelial cells (IEC) to promote viral reservoir (VR) latency or reactivation, with TNF-activated IEC limiting HIV outgrowth in CD4+ T cells of people with HIV (PWH) on antiretroviral therapy (ART). The pro-latency effect of TNF coincided with the induction of IL-32, a pro-inflammatory cytokine overexpressed in ART-treated PWH. Since type I IFNs are strong modulators of IL-32, we investigated IFN-β ability to modulate the crosstalk between IEC and CD4+ T cells via IL-32-dependent mechanisms.