Research Progress on the GP5a Protein of Porcine Reproductive and Respiratory Syndrome Virus: Molecular Characteristics, Genetic Evolution, Biological Functions, and Applications

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, remains a major threat to the global swine industry, and current control relies mainly on vaccination. GP5a, encoded by ORF5a, is a newly identified non-glycosylated envelope structural protein of PRRSV. This review summarizes published studies on the discovery, molecular characteristics, genetic evolution, biological functions, and applications of GP5a, with emphasis on its sequence variation, interactions with host and viral proteins, roles in replication and virulence, and co-evolution with GP5. GP5a is approximately 5–6 kDa and is the smallest PRRSV structural protein. Although relatively conserved, it shows amino acid variations mainly in transmembrane and intramembrane domains. GP5a interacts with host proteins and viral nonstructural proteins, participates in replication and transcription, regulates virulence, and influences immune responses. Silencing GP5a markedly reduces viral titers, and GP5a mutations are associated with attenuation and virulence reversion. GP5a co-evolves with GP5 through overlapping ORF5a/ORF5 and codon usage balance. Its immunogenicity and conserved epitopes make it a potential target for vaccines, diagnostics, and antiviral drugs, although neutralizing antibodies induced by GP5a are limited. Its structure, interactome, and precise molecular mechanisms should be clarified in further studies.