Background: The role of the mucosal microbiome in viral infections remains unclear. Genital herpes, caused by herpes simplex virus 1 and 2 (HSV-1 and HSV-2), is among the most prevalent sexually transmitted infections. Despite evidence linking vaginal Lactobacillus to protection against viral infection, the specific mechanisms mediating this defense are not well understood.

Results: Here, we show that multiple cell wall components from gram-positive bacteria, including lactobacilli, inhibit HSV-1 and HSV-2 infection in cells and in a mouse model of genital herpes infection. Peptidoglycan and lipoteichoic acid, significantly reduced HSV infectivity in cells and improved disease outcomes in mice. Antiviral effects of cell wall components relied on intact PG structure and were independent of TLR2-mediated host signaling.

Conclusions: Our findings identify a species-independent antiviral function for multiple gram-positive bacterial cell wall components against HSV-1 and HSV-2 infection and suggest that the composition of the mucosal microbiome may play an underappreciated role in suppressing mucosal herpes infection in humans.