Myriocin Promotes Herpes Simplex Virus Replication

Herpes simplex virus1and2(HSV-1and HSV-2), also known as human herpes virus1and2(HHV1and HHV2), are members of the Herpesviridae family. Both HSV-1and HSV-2are transmitted through infection of mucosal epithelia with HSV-1as a major cause of mouth blisters and HSV-2a major pathogen of genital infection. Both HSV-1and HSV-2undergo productive infection and latent infection. The mechanisms regulating HSV replication and reactivation are less understood.During the screening of antiviral natural products, we identified myriocin, a fungal metabolite, which selectively promotes both HSV-1(strains17and8F) and HSV-2(strain G) replication and ICPO protein expression in Vero cells and, to a less degree, in SK-N-SH neuronal cells at nanomolar concentrations. No effect on several DNA and RNA viruses was observed.Myriocin is a selective inhibitor of sphingolipid biosynthesis. Addition of structurally different inhibitors of sphingolipid metabolism pathway however did not promote HSV replication. Inhibitors of histone deacetylase are the only known compounds that are known to promote HSV replication. Treatment of Vero cells with myriocin did not significantly promote histone H3acetylation. Here we report the enhancement effect of myriocin on HSV infection.