Kristina Broliden

Purpose and Aim: This project aims to address critical gaps in understanding host susceptibility to sexually transmitted viral infections. Using HIV as a model of a sexually transmitted viral infection of pandemic concern, we will identify viral entry mechanisms at the genital mucosa during the initial days to weeks following primary infection. Project Plan: Vaginal tissue samples have been collected from clinical cohorts of women representing populations experiencing social inequalities, including female sex workers and young women from Sub-Saharan Africa. A multi-omics approach will be employed to analyze these samples, incorporating spatial transcriptomics, multiplex imaging analysis, and in situ hybridization. Mechanisms of HIV susceptibility will be identified by comparing women at high risk of infection due to an anaerobic polymicrobial cerivocvaginal microbiome with those having a Lactobacillus-dominated micorbiome. The cellular and molecular landscape of acute HIV infection will be assessed by co-staining for viral RNA/DNA and host mucosal markers.Significance: The findings will guide the development of novel prophylactic compounds to establish a protective genital mucosal barrier, significantly reducing the risk of viral transmission. Potential treatments may include immunomodulatory, live biotherapeutic, or hormone therapies to enhance mucosal barrier integrity, offering broad-spectrum efficacy against various viral infections of pandemic concern.