PMID:17804495

Citation	Lochridge, VP and Hardy, ME (2007) A single-amino-acid substitution in the P2 domain of VP1 of murine norovirus is sufficient for escape from antibody neutralization. J. Virol. 81:12316-22
Abstract	Noroviruses cause epidemic outbreaks of acute viral gastroenteritis worldwide, and the number of reported outbreaks is increasing. Human norovirus strains do not grow in cell culture. However, murine norovirus (MNV) replicates in the RAW 264.7 macrophage cell line and thus provides a tractable model to investigate norovirus interactions with host cells. Epitopes recognized by monoclonal antibodies (MAbs) against the human norovirus strains Norwalk virus and Snow Mountain virus (SMV) identified regions in the P domain of major capsid protein VP1 important for interactions with putative cellular receptors. To determine if there was a relationship between domains of MNV VP1 and VP1 of human norovirus strains involved in cell binding, epitope mapping by phage display was performed with an MNV-1-neutralizing MAb, A6.2.1. A consensus peptide, GWWEDHGQL, was derived from 20 third-round phage clones. A synthetic peptide containing this sequence and constrained through a disulfide linkage reacted strongly with the A6.2.1 MAb, whereas the linear sequence did not. Four residues in the A6.2.1-selected peptide, G327, G333, Q334, and L335, aligned with amino acid residues in the P2 domain of MNV-1 VP1. This sequence is immediately adjacent to the epitope recognized by anti-SMV MAb 61.21. Neutralization escape mutants selected with MAb A6.2.1 contained a leucine-to-phenylalanine substitution at position 386 in the P2 domain. The predicted location of these residues on VP1 suggests that the phage peptide and the mutation in the neutralization-resistant viruses may be in close proximity to each other and to residues reported to be important for carbohydrate binding to VP1 of human norovirus strains.
Links	PubMed PMC2168968 Online version:10.1128/JVI.01254-07
Keywords	Amino Acid Motifs; Amino Acid Sequence; Amino Acid Substitution; Animals; Antibodies, Monoclonal/immunology; Antibodies, Viral/immunology; Epitope Mapping; Epitopes/chemistry; Epitopes/genetics; Epitopes/immunology; Humans; Mice; Molecular Sequence Data; Mutation; Neutralization Tests; Norovirus/chemistry; Norovirus/immunology; Norwalk virus/chemistry; Norwalk virus/immunology; Peptide Library; Protein Conformation; Protein Structure, Tertiary; Viral Core Proteins/chemistry; Viral Core Proteins/genetics; Viral Core Proteins/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
9CALI:Q2V8W4	involved_in	GO:0019049: evasion or tolerance of host defenses by virus	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
9CALI:Q2V8W4		GO:0019049: evasion or tolerance of host defenses by virus	ECO:0000315:		P		Figure 3.	complete CACAO 8321

References

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