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Journal of Virology, July 2008, p. 6689-6696, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00160-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

L. M. Smith,1,2 A. R. McWhorter,1,2 L. L. Masters,1,2 G. R. Shellam,1,2 and A. J. Redwood1,2*

Discipline of Microbiology and Immunology, School of Biomedical, Biochemical and Chemical Sciences, MDP M502, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia,1 Marshall Centre for Infectious Diseases Research and Training, School of Biomedical, Biochemical and Chemical Sciences, MDP M502, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia2

Received 22 January 2008/ Accepted 4 April 2008

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.

* Corresponding author. Mailing address: Discipline of Microbiology and Immunology, M502, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Phone: 61(0)8 9346 2512. Fax: 61(0)8 9346 2912. E-mail: aredwood{at}cyllene.uwa.edu.au

{triangledown} Published ahead of print on 16 April 2008.

Journal of Virology, July 2008, p. 6689-6696, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00160-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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