Etude de la transmission du gammaherpèsvirus murin 4: importance de la glycoprotéine gp150 et développement de stratégies antivirales basées sur l'utilisation du cidofovir

Gammaherpèsviruses are important pathogens in human medicine. Indeed, Epstein Barr virus and Kaposi Sarcoma associated herpesvirus are responsible for numerous lymphoproliferative diseases and cancers. Murid Herpesvirus-4 (MuHV-4) is usually used as a model for human gammaherpèsviruses. Until now, the major limitation of this model was the absence of transmission in laboratory animals. Recently, a sexual transmission of MuHV-4 has been described in laboratory mice. This observation allows, on the one hand, to study mechanisms underlying natural transmission, such as cellular trospism, importance of viral proteins, or immunity response during this part of the cycle. On the other hand, this transmission model allows to test efficiency of measures to reduce transmission. Indeed, herpesvirus are archetype of persistant viruses as infection persists lifelong once established. Studying mechanisms underlying transmission and how to use these mechanisms to reduce it efficiently is therefore of primordial importance.
In a first study, we focussed on the biological relevance of mechanisms described previously in vitro. Indeed, a MuHV-4 glycoprotein, gp150, has been shown to participate to the release of infectious particles from cells and to evasion of humoral immunity, two functions that could be important for the virus during transmission. Our results showed that gp150 is essential for an efficient sexual transmission of the MuHV-4. Indeed, gp150 promotes the release of infectious particles from infected vaginal epithelial cells. These results has been published in Journal of Virology in July 2017.
In a second study, the same model was used to test efficiency of an antiviral molecule to reduce sexual transmission of the MuHV-4. A nucleotide analogue, the cidofovir, was administrated to mice according to different protocols. A daily administration of cidofovir reduced drastically genital shedding, but also prevent completely infection of naive mice after sexual contact. Finally, a single injection of cidofovir, administered 24 hours after sexual contact, reduced significantly transmission.
Altogether, in this work, we used a transmission model of a gammaherpèsvirus in two differents studies: the first foccused on glycoprotein implicated during the transmission and established the importance of a single viral glycoprotein for an efficient transmission. The second study highlighted the efficiency of antiviral drugs to prevent infection by gammaherpesviruses.