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

Abstract

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.