Characterization of a novel conformational GII.4 norovirus epitope: Implications for norovirus-host interactions

Noelia Carmona-Vicente, Susana Vila-Vicent, David Allen, Roberto Gozalbo-Rovira, Miren Iturriza-Go'Mara, Javier Buesa, Jesús Rodríguez-Díaz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predicted epitope is composed of 11 amino acids within the P domain: P245, E247, I389, Q390, R397, R435, G443, Y444, P445, N446, and D448. Only two of them, R397 and D448, differ from the homologous variant (GII.4 Den-Haag_2006b) and from a previous variant (GII.4 VA387_1996) that is not recognized by the antibody. A double mutant derived from the VA387_1996 variant containing both changes, Q396R and N447D, is recognized by the 3C3G3 monoclonal antibody, confirming the participation of the two sites in the epitope recognized by the antibody. Furthermore, a single change, Q396R, is able to modify the histo-blood group antigen (HBGA) recognition pattern. These results provide evidence that the epitope recognized by the 3C3G3 antibody is involved in the virus-host interactions, both at the immunological and at the receptor levels.

Original languageEnglish
Pages (from-to)7703-7714
Number of pages12
JournalJournal of Virology
Volume90
Issue number17
DOIs
Publication statusPublished - 2016

Bibliographical note

Funding Information:
This work, including the efforts of Jes?s Rodr?guez-D?az, was funded by Ministerio de Econom?a y Competitividad (MINECO) (RYC-2013-12442 and AGL2014-52996-C2-2-R). This work, including the efforts of Javier Buesa, was funded by Ministerio de Econom?a y Competitividad (MINECO) (SAF2012-38368). This work, including the efforts of Noelia Carmona- Vicente, was funded by Universitat de Val?ncia (V Segles fellowship).

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