Murine gammaherpesvirus (MHV) MK3 gene sequence diversity among 72, 4556, and 68 strains.

Murid herpesvirus 4 (MuHV-4) currently serves as a model for study of human gamma-herpesvirus pathogenesis. It codes for MK3 protein that similarly as K5 protein of Kaposi's sarcoma-associated herpesvirus are members of a family of structurally related viral immune evasion molecules possessing RING-CH finger domain with ubiquitin ligase activity. Murine herpesvirus 72 (MHV-72) isolated from the same species of free-living small rodent is considered as closely related to Murine herpesvirus 68 (MHV-68). Studies on MHV-72, identified dissimilarity from MHV-68 in the sequence of glycoprotein 150 [K. Macáková, J. Matis, I. Rezuchová, O. Kúdela, H. Raslová, M. Kúdelová, Virus Genes 26, 89-95 (2003)]. Murine herpesvirus 4556 (MHV-4556) is relatively new, till now, uncharacterised strain isolated from different murid species Apodemus flavicollis. We have therefore sequenced the MK3 gene of MHW-72 as well as of MHV-4556 to find out the evidence of their difference from that of MHV-68. We show here the unique nucleotide mutation in MHV-72 MK3 gene changing the codon at C-end of MK3 protein that was earlier predicted to function in interaction with TAP1/2. Furthermore, one from two nucleotide mutations found for MHV-4556 MK3 gene changed the codon that is localized at N-terminus of MK3 protein. MHV-4556-specific mutation was found within MK3 RING-CH finger domain known to be necessary for the ubiquitination of MHC class I proteins. Moreover, the latter established the new restriction site specific for MHV-4556.

Murine gammaherpesvirus (MHV) M7 gene encoding glycoprotein 150 (gp150): difference in the sequence between 72 and 68 strains.

Murine gamma herpesvirus 72 (MHV-72) was isolated from the same species of free-living small rodent as MHV-68 which currently serves as a model for study of human gamma-herpesvirus pathogenesis. MHV-68 open reading frame (ORF) M7 encodes a virus-associated transmembrane glycoprotein 150 (gp150) and displays sequence homology with Epstein-Barr virus (EBV) membrane antigen gp350/220. MHV-68 was used to model potential efficacy of EBV gp350 as an immunogen to protect against virus-associated disease. Studies on MHV-72, which is considered as closely related to MHV-68, identified some dissimilarity from MHV-68. By the contrast to MHV-68, abnormal lymphocytes have been described after infection with MHV-72. We have therefore sequenced the MHV-72 gp150 gene to find out the evidence of difference from that of MHV-68. We show here that from five nucleotide mutations found four changed the codon. Three codon changes are mapped out of two gp150 transmembrane domains and out of proline rich repeat region, respectively. Possible changes in the predicted secondary structure are discussed.