Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis

Macrae, A.I., Dutia, B.M., Milligan, S., Brownstein, D.G., Allen, D.J., Mistrikova, J., Davison, A.J. , Nash, A.A. and Stewart, J.P. (2001) Analysis of a novel strain of murine gammaherpesvirus reveals a genomic locus important for acute pathogenesis. Journal of Virology, 75(11), pp. 5315-5327. (doi: 10.1128/jvi.75.11.5315-5327.2001)

Abstract

Infection of mice by murine gammaherpesvirus 68 (MHV-68) is an excellent small-animal model of gammaherpesvirus pathogenesis in a natural host. We have carried out comparative studies of another herpesvirus, murine herpesvirus 76 (MHV-76), which was isolated at the same time as MHV-68 but from a different murid host, the yellow-necked mouse (Apodemus flavicollis). Molecular analyses revealed that the MHV-76 genome is essentially identical to that of MHV-68, except for deletion of 9,538 bp at the left end of the unique region. MHV-76 is therefore a deletion mutant that lacks four genes unique to MHV-68 (M1, M2,M3, and M4) as well as the eight viral tRNA-like genes. Replication of MHV-76 in cell culture was identical to that of MHV-68. However, following infection of mice, MHV-76 was cleared more rapidly from the lungs. In line with this, there was an increased inflammatory response in lungs with MHV-76. Splenomegaly was also significantly reduced following MHV-76 infection, and much less latent MHV-76 was detected in the spleen. Nevertheless, MHV-76 maintained long-term latency in the lungs and spleen. We utilized a cosmid containing the left end of the MHV-68 genome to reinsert the deleted sequence into MHV-76 by recombination in infected cells, and we isolated a rescuant virus designated MHV-76(cA8+)4 which was ostensibly genetically identical to MHV-68. The growth properties of the rescuant in infected mice were identical to those of MHV-68. These results demonstrate that genetic elements at the left end of the unique region of the MHV-68 genome play vital roles in host evasion and are critical to the development of splenic pathology.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Milligan, Mr Steve and Davison, Professor Andrew
• Authors: Macrae, A.I., Dutia, B.M., Milligan, S., Brownstein, D.G., Allen, D.J., Mistrikova, J., Davison, A.J., Nash, A.A., and Stewart, J.P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Virology
• Journal Abbr.: J. Virol.
• ISSN: 0022-538X
• ISSN (Online): 1098-5514