Evolution of porcine reproductive and respiratory syndrome virus GP5 and GP3 genes under swIFN-β immune pressure and interferon regulatory factor-3 activation suppressed by GP5

• swIFN promotes PRRSV GD high variability in GP5.
• GP5 inhibits IRF3 from phosphorylation to escape from swIFN-β.
• PRRSV GD propagated in Marc-145 cell cultures with swIFN-β has stronger inhibitory effect on the swIFN-β response.

In this study, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) strain, PRRSV GD07 was continuously propagated in MARC-145 cell cultures primed with swIFN-β for 50 passages to develop the PRRSV GDβfn strains. And a control strain PRRSV GDfn was passaged without swIFN-β. The sequencing analysis indicated that under swIFN-β immune pressure, molecular variation of PRRSV GP5 was accelerated in gene (NS/S > 2.50), and the acceleration of GP3 was not significant (NS/S < 2.50). swIFN-β mRNA level induced by Poly(I:C) is lower in cells primed with PRRSV GDβfn than in cells without PRRSV GDfn, although both of them are much less than the control group. Effect of GP5 on IRF3 was analyzed by SDS-PAGE and western-blot. Our results indicated that GP5 protein prevents IRF3 phosphorylation. Therefore, we conclude that swIFN can promote viral mutation in GP5, and, in turn GP5 inhibits IRF3 activation to escape from swIFN-β.