Determining the epitope dominance on the capsid of a SAT2 foot-and-mouth disease virus by mutational analyses

OPPERMAN, PAMELA; ROTHERHAM, LIA; ESTERHUYSEN, JAN; CHARLESTON, BRYAN; JULEFF, NICHOLAS; CAPOZZO, ALEJANDRA VICTORIA; THERON, JACQUES; MARéE, FRANCOIS

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014

0022-538X

Monoclonal antibody resistant mutants have been traditionally used to map antigenic sites on foot-and-mouth disease virus (FMDV), of which the flexible âG-âH loop in VP1 is antigenically important. For FMDV SAT2 viruses, studies have shown that at least three antigenic sites exist. Using an infectious SAT2 cDNA clone ten structurally exposed and highly variable loops were identified as putative antigenic sites on the VP1, VP2 and VP3 capsid proteins of SAT2/ZIM/7/83 and replaced with the corresponding region of SAT2/KNP/19/89. Virus neutralization assays using convalescent antisera raised against the parental virus, SAT2/ZIM/7/83, indicated that the TQQS to ETPV mutation in the N-terminal part of the âG-âH loop of VP1, not only showed a significant increase in the neutralization titre but also an increase in the avidity index to the convalescent antisera. Furthermore, antigenic profiling of the epitope-replaced and parental viruses with non-neutralizing SAT2-specific MAbs led to the identification of two non-neutralizing antigenic regions. Both regions were mapped to incorporate residues 71-72 of VP2 as the major contact point of the four MAbs and the binding footprint of two of the MAbs encompasses residues 133-134 of VP2 and 48-50 of VP1. This is the first time an antigenic region, encompassing residues 71-72 of VP2, has been identified on the capsid of a SAT2 FMDV. In this study evidence for the structural engineering of antigenic sites of a SAT2 capsid to broaden cross-reactivity with antisera is provided.