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Journal of Virology, May 2009, p. 4092-4101, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02245-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ganglioside-Linked Terminal Sialic Acid Moieties on Murine Macrophages Function as Attachment Receptors for Murine Noroviruses{triangledown}

Stefan Taube,1 Jeffrey W. Perry,1 Kristen Yetming,1 Sagar P. Patel,1 Heather Auble,1 Liming Shu,2 Hesham F. Nawar,3 Chang Hoon Lee,3 Terry D. Connell,3 James A. Shayman,2 and Christiane E. Wobus1*

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109,1 Department of Internal Medicine, Nephrology Division, University of Michigan Medical School, Ann Arbor, Michigan 48109,2 Witebsky Center for Microbial Pathogenesis and Immunology, School of Medicine and Biomedical Sciences, Department of Microbiology and Immunology, Buffalo, New York 142143

Received 25 October 2008/ Accepted 16 February 2009

Noroviruses are the major cause of nonbacterial gastroenteritis in humans. However, little is known regarding the norovirus life cycle, including cell binding and entry. In contrast to human noroviruses, the recently discovered murine norovirus 1 (MNV-1) readily infects murine macrophages and dendritic cells in culture. Many viruses, including the related feline calicivirus, use terminal sialic acids (SA) as receptors for infection. Therefore, we tested whether SA moieties play a role during MNV-1 infection of murine macrophages. Competition with SA-binding lectins and neuraminidase treatment led to a reduction in MNV-1 binding and infection in cultured and primary murine macrophages, suggesting a role for SA during the initial steps of the MNV-1 life cycle. Because SA moieties can be attached to glycolipids (i.e., gangliosides), we next determined whether MNV-1 uses gangliosides during infection. The gangliosides GD1a, GM1, and asialo-GM1 (GA1) are natural components of murine macrophages. MNV-1 bound to ganglioside GD1a, which is characterized by an SA on the terminal galactose, but not to GM1 or asialo-GM1 in an enzyme-linked immunosorbent assay. The depletion of gangliosides using an inhibitor of glycosylceramide synthase (D-threo-P4) led to a reduction of MNV-1 binding and infection in cultured and primary murine macrophages. This defect was specifically rescued by the addition of GD1a. A similar phenotype was observed for MNV field strains WU11 (GV/WU11/2005/USA) and S99 (GV/Berlin/2006/DE). In conclusion, our data indicate that MNV can use terminal SA on gangliosides as attachment receptors during binding to murine macrophages.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 5622 Medical Sciences Bldg. II, 1150 West Medical Center Dr., University of Michigan Medical School, Ann Arbor, MI 48109-5620. Phone: (734) 647-9599. Fax: (734) 764-3562. E-mail: cwobus{at}umich.edu

{triangledown} Published ahead of print on 25 February 2009.

Journal of Virology, May 2009, p. 4092-4101, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02245-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rydell, G. E, Dahlin, A. B, Hook, F., Larson, G. (2009). QCM-D studies of human norovirus VLPs binding to glycosphingolipids in supported lipid bilayers reveal strain-specific characteristics. Glycobiology 19: 1176-1184 [Abstract] [Full Text]  


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