Comparative study of Murid gamma-herpesvirus 4 infection in mice and in a natural host, the bank voles.

Gamma-herpesviruses are archetypal pathogenic persistent viruses. The known human gamma-herpesviruses (Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus) are host-specific and therefore lack a convenient in vivo infection model. This makes related animal gamma-herpesviruses an important source of information. We are studying Murid herpesvirus 4 (MuHV-4), a virus originally isolated from bank voles (Myodes glareolus). MuHV-4 infection of inbred laboratory mouse strains (Mus musculus) is commonly used as a general model of gamma-herpesvirus pathogenesis. However, MuHV-4 has not been isolated from house mice, and no systematic comparison has been made between experimental MuHV-4 infections of mice and bank voles. We have therefore characterized MuHV-4 (strain MHV-68) infection of bank voles, both through global luciferase imaging and through classical virological methods. As in mice, intranasal virus inoculation led to productive replication in bank vole lungs, accompanied by massive cellular infiltrates. However, the extent of lytic virus replication was ~1000 fold lower in bank voles than in mice. Peak latency titers in lymphoid tissue were also lower, although latency was still established. Finally, we tested viral transmission between animals maintained in captivity. However, as observed in mice, MuHV-4 did not transmit between voles in these conditions. In conclusion, this study revealed that despite quantitative differences, replication and latency sites of MuHV-4 are comparable in bank voles and in mice. It appears therefore so far that Mus musculus represents a suitable host for studying gamma-herpesvirus pathogenesis with MuHV-4. Establishing transmission conditions in captivity will be a vital step for further research in that field