Role of viral glycoprotein 2a (GP2a) in PRRSV infection

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major cause of economic loss in swine production, driven in part by suboptimal protective immunity and incomplete understanding of viral entry and immune evasion. This review highlights the minor envelope glycoprotein GP2a, a key component of the GP2a–GP3–GP4 heterotrimer required for production of infectious virions and infection of porcine macrophages. We summarize GP2a structural and biosynthetic features and discuss how sequence variability and glycan-dependent maturation may influence folding, heterotrimer assembly, and infectivity. We then integrate evidence linking GP2a to CD163-dependent entry and recent findings showing that specific GP2a residues modulate macrophage tropism, virulence, and cell-culture adaptation. Finally, we review emerging mechanisms demonstrating that GP2a is both targeted by host restriction pathways via ubiquitin- and autophagy/lysosome-associated degradation and functions as an innate immune antagonist by suppressing type I interferon induction through disruption of RIG-I–like receptor signaling. Together, these advances position GP2a at the intersection of receptor engagement, tropism, and host immune control, supporting GP2a-directed vaccines and antiviral strategies as promising next-generation approaches for PRRSV control. • GP2a is a key glycoprotein required for PRRSV infection. • GP2a links receptor engagement, tropism, and host restriction during PRRSV infection. • Targeting GP2a–host interactions may enable new PRRSV vaccines and antivirals.