title: Murine noroviruses bind glycolipid and glycoprotein attachment receptors in a strain-dependent manner.
abstract: Human norovirus infections are the most common cause of acute nonbacterial gastroenteritis in humans worldwide, and glycan binding plays an important role in the susceptibility to these infections. However, due to the lack of an efficient cell culture system or small animal model for human noroviruses, little is known about the biological role of glycan binding during infection. Murine noroviruses (MNV) are also enteric viruses that bind to cell surface glycans, but in contrast to their human counterparts, they can be grown in tissue culture and a small animal host. In this study, we determined glycan-binding specificities of the MNV strains MNV-1 and CR3 in vitro, identified molecular determinants of glycan binding, and analyzed infection in vivo. We showed that unlike MNV-1, CR3 binding to murine macrophages was resistant to neuraminidase treatment and glycosphingolipid depletion. Both strains depended on N-linked glycoproteins for binding, while only MNV-1 attachment to macrophages was sensitive to O-linked glycoprotein depletion. In vivo, CR3 showed differences in tissue tropism compared to MNV-1 by replicating in the large intestine. Mapping of a glycan-binding site in the MNV-1 capsid by reverse genetics identified a region topologically similar to the histo-blood group antigen (HBGA)-binding sites of the human norovirus strain VA387. The recombinant virus showed distinct changes in tissue tropism compared to wild-type virus. Taken together, our data demonstrate that MNV strains evolved multiple strategies to bind different glycan receptors on the surface of murine macrophages and that glycan binding contributes to tissue tropism in vivo.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Taube
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Perry
authors.forename: Eoghan
authors.initials: E
authors.lastname: McGreevy
authors.forename: Kristen
authors.initials: K
authors.lastname: Yetming
authors.forename: Cheryl
authors.initials: C
authors.lastname: Perkins
authors.forename: Kenneth
authors.initials: K
authors.lastname: Henderson
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Wobus
mesh_terms: D000818:Animals; D017250:Caliciviridae Infections / Q000378:metabolism* / Q000821:virology; D006017:Glycolipids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D029322:Norovirus / Q000235:genetics / Q000502:physiology*; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D013045:Species Specificity; D053585:Virus Attachment
chemical_list: D006017:Glycolipids; D006023:Glycoproteins; D011134:Polysaccharides; D011991:Receptors, Virus