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Journal of Virology, October 2007, p. 10460-10473, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00783-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Murine Noroviruses Comprising a Single Genogroup Exhibit Biological Diversity despite Limited Sequence Divergence{triangledown} ,{dagger}

Larissa B. Thackray,1 Christiane E. Wobus,1,{ddagger} Karen A. Chachu,1 Bo Liu,1 Eric R. Alegre,2 Kenneth S. Henderson,3 Scott T. Kelley,2 and Herbert W. Virgin IV1*

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110,1 Department of Biology, San Diego State University, San Diego, California 92182,2 Research Animal Diagnostic Services, Charles River Laboratories, Wilmington, Massachusetts 018873

Received 11 April 2007/ Accepted 16 July 2007

Viruses within the genus Norovirus of the family Caliciviridae are the major cause of acute, nonbacterial gastroenteritis worldwide. Human noroviruses are genetically diverse, with up to 57% divergence in capsid protein sequences, and comprise three genogroups. The significance of such genetic diversity is not yet understood. The discovery of murine norovirus (MNV) and its ability to productively infect cultured murine macrophages and dendritic cells has provided an opportunity to determine the functional consequences of norovirus diversity in vitro and in vivo. Therefore, we compared the full-length genomes of 21 new MNV isolates with five previously sequenced MNV genomes and demonstrated a conserved genomic organization consisting of four open reading frames (ORFs) and a previously unknown region of nucleotide conservation in ORF2. A phylogenetic analysis of all 26 MNV genomes revealed 15 distinct MNV strains, with up to 13% divergence at the nucleotide level, that comprise a single genotype and genogroup. Evidence for recombination within ORF2 in several MNV genomes was detected by multiple methods. Serological analyses comparing neutralizing antibody responses between highly divergent strains suggested that the MNV genogroup comprises a single serotype. Within this single genogroup, MNV strains exhibited considerable biological diversity in their ability to grow in culture and to infect and/or persist in wild-type mice. The isolation and characterization of multiple MNV strains illustrate how genetic analysis may underestimate the biological diversity of noroviruses and provide a molecular map for future studies of MNV biology.

* Corresponding author. Mailing address: Department of Pathology and Immunology, Box 8118, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. E-mail: virgin{at}wustl.edu

{triangledown} Published ahead of print on 25 July 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109.

Journal of Virology, October 2007, p. 10460-10473, Vol. 81, No. 19
0022-538X/07/$08.00+0     doi:10.1128/JVI.00783-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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