Viral glycoprotein gp150 promotes sexual transmission of Murid Herpesvirus-4

Gammaherpesviruses are important pathogens in human and veterinary medicine. During co-evolution with their hosts, they developed many strategies allowing them to shed infectious particles in presence of immune response. Understanding these strategies is likely to be important to control infection. Interestingly, we recently observed that Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus infecting laboratory mice, could be sexually transmitted between mice. This model offers therefore the opportunity to understand the mechanisms underlying natural transmission. Some of these mechanisms could rely on the glycoprotein 150 (gp150), which could limit virus neutralization and promote the release of infectious particles from cells. In this study, we tested therefore the importance of gp150 in the context of MuHV-4 sexual transmission. Briefly, female mice were infected with WT or gp150- strains expressing luciferase. They were imaged with an in vivo imaging system to follow infection. When lytic replication was observed in the genital tract, infected females were mated with naïve males to compare the capacity of transmission of the two strains. Our results show that, while the gp150- strain has no deficit in reaching and replicating in the female genital tract, it displays a major deficit of sexual transmission in comparison with WT virions. Interestingly, this deficit appears to reflect a deficit of virions release from vaginal epithelial cells. Altogether, our results show that, while gp150 is not required for efficient dissemination and maintenance of MuHV-4 within its host, it is essential for efficient transmission, by promoting the releasing of infectious particles from the mucosal cells.