Porcine reproductive and respiratory syndrome virus (PRRSV) has been the most significant disease affecting swine in the U.S. for decades. Contemporary epidemiological methods rely on sequencing of the GP5 gene which encodes the major envelope glycoprotein GP5. While some studies have corroborated the importance of GP5 for PRRSV immunity, numerous studies have suggested that the minor glycoproteins encoded by GP2a, GP3, and GP4, play critical roles in PRRSV immunity and pathogenesis, although a paucity of studies have investigated the minor glycoproteins as compared to GP5. Here, using reverse genetics, we replaced the region of the genome encoding either the minor (GP2a-GP3-GP4) or major (GP5-M) proteins of the lab strain SD95-21 with various alleles determined from contemporary circulating PRRSV. Using indirect immunofluorescence and serum neutralization assays, we show that replacement of either the minor or major proteins of PRRSV variably affects the antigenicity of PRRSV. These results illustrate the importance of considering regions of the PRRSV genome besides GP5 when evaluating PRRSV epidemiology and immunity.
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