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Journal of Virology, August 2006, p. 7322-7331, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00233-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

C-Terminal Arginine Cluster Is Essential for Receptor Binding of Norovirus Capsid Protein

Ming Tan,1 Jarek Meller,2 and Xi Jiang1*

Division of Infectious Diseases,1 Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio2

Received 1 February 2006/ Accepted 16 May 2006

Noroviruses are the major viral pathogens of epidemic acute gastroenteritis affecting people worldwide. They have been found to recognize human histo-blood group antigens as receptors. The P domain of norovirus capsid protein was found to be responsible for binding to viral receptors, and the recombinant P protein forms P dimers and P particles in vitro. In this study, we demonstrate that a highly conserved arginine (R) cluster at the C terminus of the P domain is critical for receptor binding and P particle formation of the P proteins. Deletions of the R cluster abolished these functions. Replacement of the R cluster with histidines (another positively charged amino acid) resulted in low efficiency of receptor binding and P particle formation, while replacement with alanines led to loss of both functions completely. The R cluster also contains a highly conserved trypsin digestion site. A treatment of capsid protein or P domain mutants from both genogroup I (Norwalk virus) and genogroup II (VA387) noroviruses with trypsin resulted in a removal of the R cluster and the S domain, leaving a P polypeptide of 31.3 kDa (Norwalk virus) or 34.3 kDa (VA387), similar to the soluble P protein found in vivo. Our findings imply that the proteolytic process could be a necessary step for norovirus replication in the host.

* Corresponding author. Mailing address: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Phone: (513) 636-0119. Fax: (513) 636-7655. E-mail: jason.jiang{at}cchmc.org.

Journal of Virology, August 2006, p. 7322-7331, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.00233-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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