Role of Glycoprotein 3 in neutralizing antibody recognition of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) has been causing significant economic losses in the global swine industry since its emergence. Insufficient knowledge of the structural glycoprotein characteristics of NADC30-like strains has hindered the development of effective control strategies. In this study, we found that the neutralizing antibodies (NAbs) in pig sera against NADC30-like PRRSV strain FJ1402 (lineage 1) and highly pathogenic PRRSV (HP-PRRSV) strain BB0907 (lineage 8) exhibited low cross-neutralizing activity against each other. Subsequently, six chimeric recombinant viruses were generated based on the infectious cDNA clone of HP-PRRSV strain BB0907, in which specific structural protein genes were replaced by those from the NADC30-like strain. Cross-neutralization assays revealed that the NAbs against NADC30-like strain primarily target glycoprotein 3 (GP3), glycoprotein 4 (GP4), and glycoprotein 5 (GP5). Furthermore, we constructed six additional infectious cDNA clones with point mutations in GP3, and found that the residues 66I and 85S in GP3 play critical roles during NAbs recognition. These findings provide molecular insights into the host neutralizing antibody recognition against PRRSV, highlighting the role of GP3 in the recognition process. This study offers a foundation for rational antigen selection strategies in developing PRRSV NADC30-like strain vaccines.