1. The full-length nsp2 replicase contributes to viral assembly in highly pathogenic PRRSV-2.
- Author
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Bai Y-Z, Wang S, Sun Y, Liu Y-G, Zhang H-L, Wang Q, Huang R, Rao C-H, Xu S-J, Tian Z-J, An T-Q, Cai X-H, and Tang Y-D
- Subjects
- Animals, Swine, Porcine Reproductive and Respiratory Syndrome virology, Porcine Reproductive and Respiratory Syndrome metabolism, Cell Line, Nucleocapsid Proteins metabolism, Nucleocapsid Proteins genetics, Virus Replication, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum virology, RNA-Dependent RNA Polymerase metabolism, RNA-Dependent RNA Polymerase genetics, Porcine respiratory and reproductive syndrome virus genetics, Porcine respiratory and reproductive syndrome virus metabolism, Viral Envelope Proteins metabolism, Viral Envelope Proteins genetics, Virus Assembly, Viral Nonstructural Proteins metabolism, Viral Nonstructural Proteins genetics
- Abstract
Porcine reproductive and respiratory syndrome viruses (PRRSVs) are significant pathogens that affect the global swine industry. Its virions consist of a central core composed of nucleocapsid (N) protein, surrounded by multiple distinct viral envelope proteins. However, the mechanisms underlying the recognition and packaging of N protein by viral envelope proteins remain elusive. In this study, we elucidated the role of nonstructural protein 2 (nsp2) from highly pathogenic PRRSV-2 (HP-PRRSV-2) in viral assembly. Firstly, among all the tested envelope proteins, only glycoprotein 5 (GP5) exhibits limited interaction with N protein. Interestingly, we demonstrated that full-length nsp2 co-immunoprecipitates (Co-IPs) with the N protein and all tested viral envelope proteins. In the presence of full-length nsp2, the N protein interacts with distinct viral envelope proteins. Moreover, upon viral infection, Co-IP experiments using nsp2-specific antibodies or N-specific antibodies revealed the formation of a complex between N and nsp2 with the M protein, GP2a, and GP5. However, neither of the two short forms of nsp2-namely nsp2TF nor nsp2N-participates in this process as they fail to interact with the N protein. Finally, our results demonstrate that this process occurs in the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC). Overall, our findings unveil a novel functional role for full-length nsp2 of HP-PRRSV-2 in facilitating the assembly of the N protein with viral envelope proteins.IMPORTANCEThe virus assembly process of arteriviruses remains largely elusive, including the direct interaction between N protein and viral envelope proteins or the potential requirement for additional proteins in facilitating assembly. Moreover, where the N protein assembles with viral envelope proteins during the virus lifecycle remains unclear. This study reveals a novel role for nonstructural protein 2 (nsp2) in highly pathogenic porcine reproductive and respiratory syndrome virus type 2 (HP-PRRSV-2), highlighting its involvement in HP-PRRSV-2 assembly. These findings provide crucial insights into HP-PRRSV-2 assembly and enhance our understanding of their lifecycle. Overall, this study offers an alternative approach to developing a new antiviral strategy targeting PRRSV-2 assembly., Competing Interests: The authors declare no conflict of interest.
- Published
- 2025
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