State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
School of Advanced Agricultural Sciences, Yibin Vocational and Technical College, Yibin 644000, China.
Viruses. 2024 Apr 25;16(5):678. doi: 10.3390/v16050678.
Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus's nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection.
猪繁殖与呼吸综合征病毒（PRRSV）属于冠状病毒科，是全球养猪业的持续性威胁，可导致猪只繁殖失败和呼吸道疾病。在本研究中，我们探讨了组蛋白去乙酰化酶（HDAC2）在 PRRSV 感染过程中的作用。研究结果表明，PRRSV 感染可下调 HDAC2 的表达。值得注意的是，通过特异性小干扰 RNA 抑制 HDAC2 活性会导致病毒产量增加，而过表达 HDAC2 可通过增强 IFN 调节的抗病毒分子的表达有效抑制 PRRSV 复制。此外，我们发现病毒的非结构蛋白 11（nsp11）是降低 HDAC2 水平的关键因素。PRRSV nsp11 的诱变分析表明，其对 HDAC2 抗病毒活性的拮抗作用依赖于其内切酶活性。总之，本研究揭示了 PRRSV 采用的一种新的免疫逃避机制，为该病毒的发病机制提供了重要见解，并为 PRRSV 感染的创新预防策略的开发提供了指导。
