Bacteria-virus interactions in the vaginal microbiome reduce herpes virus infectivity

The vaginal microbiome is an important determinant of host health and the first barrier encountered by sexually transmitted pathogens during infection. Among the vaginal microbiome, Lactobacilli are associated with reduced susceptibility to viral infection, but the mechanisms by which various Lactobacilli strains reduce viral infectivity remain poorly understood. Using a collection of human vaginal microbial strains, we show that the prominent vaginal strain, Lactobacillus crispatus reduces infectivity of sexually transmitted pathogen Herpes Simplex Virus (HSV). Reduction of HSV infectivity is species specific, with L. crispatus reducing infection and disease better than gut-associated L. reuteri. Active cell metabolism is not required as UV-killed L. crispatus retain the ability to reduce herpes infection. Since one of the most abundant structures on the outside of the L. crispatus cell is peptidoglycan, we assessed whether peptidoglycan could reduce HSV infection. We found that commercially available purified peptidoglycan from multiple bacterial sources reduced herpes infection in vitro and in vivo in a mouse model of genital herpes infection. Mice were susceptible to reinfection, indicating that immunological memory is not activated. Cleavage of the glycosidic linkages in the peptidoglycan chain with lysozyme restored virus infectivity in vitro and in vivo suggesting that antiviral effects are dependent on longer peptidoglycan chains. Current studies aim to determine how Lactobacilli peptidoglycan contributes to a reduction in HSV infectivity focusing on HSV entry receptors and what species-specific peptidoglycan modifications allow L. crispatus to reduce infectivity better than other Lactobacilli. Such results provide a greater understanding of the ways that the vaginal microbiome serves as a physical barrier to infection and why some vaginal communities promote better antiviral protection than others.