Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV) that is characterized by a highly variable gene sequence and a high rate of recombination, thereby contributing to difficulties in the clinical prevention and control of this virus. Glycosylated protein 3 (GP3) is the most glycosylated protein in PRRSV, and is closely associated with the composition of PRRSV virus particles, infection, and immune evasion. This review summarizes the structural features, genetic evolutionary patterns, glycosylation of GP3 and its interactions with other PRRSV and host proteins, associations with PRRSV infection and virulence, and immunomodulatory roles. Additionally, it provides an overview of research progress on monoclonal antibodies and vaccines targeting GP3. This study aims to provide a theoretical foundation for better understanding the structure and function of GP3, of the mechanisms of PRRSV infection, and the development of novel vaccines.

Background: Porcine reproductive and respiratory syndrome (PRRS) has been present in China for about 30 years, and because of the high mutability of PRRSV, it causes huge economic losses to pig enterprises every year. PRRSV-2 is widely prevalent in China, and the detection rate of PRRSV-1 is also on the rise. Nonstructural protein 2 (NSP2) is a highly variable protein with multiple biological functions, such as PRRSV replication, which plays an important role in understanding PRRSV variation and epidemic alerts. Objectives: The epidemic characteristics and recombination of PRRSV-1 NSP2 are still unknown. The purpose of this study is to study the epidemic characteristics of PRRSV-1 NSP2 and lay a foundation for the prevention and control of PRRSV-1. Methods: In this study, we collected several PRRSV-1 and PRRSV-2 NSP2 gene sequences for gene sequence and recombination analyses, aiming to analyze the recombination pattern and genetic variation in the PRRSV-1 NSP2 genes in China. Results: The genetic similarity results showed that the 69 PRRSV-1 NSP2 gene sequences collected in this study showed nucleotide similarity ranging from 67.3% to 100.0% and amino acid similarity ranging from 64.3% to 100.0%. Amino acid sequence comparison showed that PRRSV-1 had more amino acid deletion or substitution sites than PRRSV-2. NSP2 also contains special amino acid regions such as the highly immunogenic region. PRRSV-1 can be categorized into four strains, NMEU09-1-like, BJEU06-1-like, HKEU-16-like and Amervac-like isolates, and are at different positions in the ML and NJ phylogenetic trees. In the ninety selected PRRSVs, six recombination events were detected using recombination analysis, two of which occurred in Chinese PRRSV-1 strains. Therefore, sequence analysis of NSP2 helps us to understand the prevalence and variation in PRRSV-1 in China over the past two decades and provides a theoretical basis for studying the epidemiology and evolution of NSP2.

Porcine reproductive and respiratory syndrome (PRRS) has been prevalent in Germany for over 30 years, posing a significant threat to the local swine industry. There are limited analyses to offer German PRRSV ORF5 genetic and evolutionary characteristics and GP5 structural and functional features. In this study, a total of 518 sequences of the PRRSV GP5 gene were obtained from the GenBank database, encompassing 102 sequences from Germany to investigate the genetic relationships and GP5 structural and functional features. Similarly, phylogenetic and recombination analyses were used to identify genetic relationships. Two German PRRSV-1 lineage 1 strains exhibited more than 98.0% nucleotide similarity with vaccine strains. Eighteen German PRRSV-2 lineage 5 strains exhibited more than 98.0% nucleotide similarity with a prototype vaccine strain. German PRRSV-1 lineage 1 was predominant. GP5 structural and functional features were determined by N-glycosylation sites, B-cell epitopes, and transmembrane domain predictions. The main N-glycosylation patterns and transmembrane domains of German PRRSV-1 lineage 1 were time-dependent. Mutations of German PRRSV-1 lineage 3 in the primary neutralizing epitope were detected. In conclusion, these findings reveal lineage-specific molecular variation and improve the understanding of the molecular evolution of German PRRSV.

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.