Virus-Bacterial interactions in genital herpes infections Mucosal viruses encounter resident bacteria before they encounter and activate the immune response and these interactions can affect viral infection and replication. These virus-bacterial interactions heavily influence viral infections in the intestinal tract but are understudied in the vaginal mucosa. Studies have shown that vaginal lactobacilli can interact with herpes simplex virus however the bacterial components involved in this interaction remain unknown. Our preliminary data show that vaginal lactobacilli interact with herpes simplex virus and inhibit infectivity to a much greater extent than gut lactobacilli. Additionally, this interaction is independent of lactic acid as dead bacteria are equivalently inhibitory. Further, we were able to mimic this interaction using peptidoglycan from non-vaginal gram-positive bacteria. In this proposal, we aim to explore the role of purified peptidoglycan from vaginal lactobacilli strains and compare their efficacy against gut lactobacilli (Aim 1). We will explore the role of peptidoglycan-sensing innate immune receptors in this viral suppression (Aim 2). We will define the relevance of these observations to human health by quantifying vaginal peptidoglycan in vaginal samples from people with lactobacilli-dominant microbiomes and bacterial vaginosis patients who have lost their vaginal lactobacilli and have been clinically shown to have increased shedding of herpes simplex virus. These experiments aim to propose a mechanistic basis for clinical observations linking abundance of vaginal lactobacilli to reduced viral infection and replication.