Laboratory Strains of Murine Cytomegalovirus Are Genetically Similar to but Phenotypically Distinct from Wild Strains of Virus

Abstract

Murine cytomegalovirus (MCMV) is widely used to model human cytomegalovirus (HCMV) infection.However, it is known that serially passaged laboratory strains of HCMV differ significantly from recently isolated clinical strains of HCMV. It is therefore axiomatic that clinical models of HCMV using serially passaged strains of MCMV may not be able to fully represent the complexities of the system they are attempting to model and may not fully represent the complex biology of MCMV. To determine whether genotypic and phenotypic differences also exist between laboratory strains of MCMV and wild derived strains of MCMV, we sequenced the genomes of three low-passage strains of MCMV, plus the laboratory strain, K181. We coupled this genetic characterization to their phenotypic characteristics. In contrast to what is seen with HCMV (and rhesus CMV), there were no major genomic rearrangements in the MCMV genomes. In addition, the genome size was remarkably conserved between MCMV strains with no major insertions or deletions. There was, however, significant sequence variation between strains of MCMV, particularly at the genomic termini. These more subtle genetic differences led to considerable differences in in vivo replication with some strains of MCMV, such as WP15B, replicating preferentially in otherwise-MCMV-resistant C57BL/6 mice. CBA mice were no more resistant to MCMV than C57BL/6 mice and for some MCMV strains appeared to control infection less well than C57BL/6 mice. It is apparent that the previously described host resistance patterns of inbred mice and MCMV are not consistently applicable for all MCMV strains.

Murine Cytomegalovirus Is Not Restricted to the House Mouse Mus musculus domesticus: Prevalence and Genetic Diversity in the European House Mouse Hybrid Zone

“…Murine cytomegalovirus 1 (MCMV), also called Murid herpesvirus 1 (MuHV-1), is a betaherpesvirus of the house mouse and one of its most studied pathogens, because it serves as a laboratory model for human cytomegalovirus (HCMV) infection, which can be highly pathogenic for immunocompromised individuals (1). Almost all laboratory research on MCMV uses either the Smith or the K181 strain of the virus (2). The Smith strain was originally isolated from salivary gland tissue of laboratory mice in the United States in 1954 (3), and the K181 strain was selected by repeated passage of the prototype Smith strain in mouse submaxillary glands (2).…”

“…Almost all laboratory research on MCMV uses either the Smith or the K181 strain of the virus (2). The Smith strain was originally isolated from salivary gland tissue of laboratory mice in the United States in 1954 (3), and the K181 strain was selected by repeated passage of the prototype Smith strain in mouse submaxillary glands (2). These strains have been serially passaged in vivo and in vitro-in the case of the Smith virus, for more than 50 years.…”

“…Apart from the two standard MCMV laboratory strains, several strains have been isolated from wild house mice in Australia, Beacon Island, and Macquarie Island, and their whole genomes have been sequenced (2,4,5). These strains are genetically different from strains Smith and K181 (4) and show in vivo replication kinetics different from those of the standard strains (5), suggesting that the patterns of host resistance to MCMV described for inbred mice are not applicable to all MCMV strains (2). All of these strains have been isolated either from a single subspecies of mouse, Mus musculus domesticus, or from lab mice, which are derived mostly from M. m. domesticus stocks (6).…”

Viral MHC Class I–like Molecule Allows Evasion of NK Cell Effector Responses In Vivo

“…Although no selfligands for activating Ly49H B6 receptors have been reported, inhibitory Ly49C-like receptors bind with high affinity to MHC-I molecules, precluding an easy assessment of additional ligand recognition during infection (15, 32). Further, inoculation of (33). This suggests that in natural settings, m157 is under both selective negative and positive pressures, depending on the NK cell repertoire and H-2 background.…”

Rat cytomegalovirus (RCMV) English isolate and a newly identified Berlin isolate share similarities with but are separate as an anciently diverged clade from Mouse CMV and the Maastricht isolate of RCMV

“…By contrast, RCMV-E encoded two orthologues of C-type lectin-like proteins, RCTL and RCTL2 (Ettinger et al, 2012;Voigt et al, 2007), which are absent in MCMV but share 48.8 and 26.8 % amino acid sequence similarity, respectively, with the only C-type lectin-like protein encoded by RCMV-M, the product of the r153 gene (Brocchieri et al, 2005). Twenty RCMV-E ORFs lacked orthologues in other CMVs including isolates from wild mice strains (Smith et al, 2008). The gene products of 2 of English and Berlin RCMV isolates form an ancient clade these 20 putative ORFs displayed high sequence similarity to cellular proteins, thereby implying that they were likely captured from the host.…”