Molecular assessment of the role of envelope-associated structural proteins in cross neutralization among different PRRS viruses

To assess the role of each envelope-associated protein (i.e., ORFs 2-6 products) of type 2 PRRSV in cross neutralization mediated by antibody, chimeric mutants were generated by replacing ORFs of a VR2332-based infectious clone with those of JA142, SDSU73, PRRS124, or 2M11715 that are genetically and antigenically distinct from VR2332 and two-way neutralization assays were performed on those mutants using VR2332, JA142, SDSU73, or PRRS124 antisera. All ORF 5-replaced mutants showed increased susceptibility or resistance against homologous or heterologous antisera, respectively, in comparison to that of the donor strains, but failed to achieve a complete reversion of cross neutralization. In contrast, substitution of ORFs 3-6 completely reversed the susceptibility of the virus to neutralization by antibody. Changes in ORFs 3, 5, and 6 were additively responsible for reversion of the susceptibility, suggesting that the genetic similarity of these ORFs should be considered for better cross neutralization between two different type 2 PRRS viruses.