State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Viruses. 2022 Feb 24;14(3):467. doi: 10.3390/v14030467.
The porcine reproductive and respiratory syndrome virus (PRRSV) remains a persistent hazard in the global pig industry. DEAD (Glu-Asp-Ala-Glu) box helicase 21 (DDX21) is a member of the DDX family. In addition to its function of regulating cellular RNA metabolism, DDX21 also regulates innate immunity and is involved in the replication cycle of some viruses. However, the relationship between DDX21 and PRRSV has not yet been explored. Here, we found that a DDX21 overexpression promoted PRRSV replication, whereas knockdown of DDX21 reduced PRRSV proliferation. Mechanistically, DDX21 promoted PRRSV replication independently of its ATPase, RNA helicase, and foldase activities. Furthermore, overexpression of DDX21 stabilized the expressions of PRRSV nsp1α, nsp1β, and nucleocapsid proteins, three known antagonists of interferon β (IFN-β). Knockdown of DDX21 activated the IFN-β signaling pathway in PRRSV-infected cells, suggesting that the effect of DDX21 on PRRSV-encoded IFN-β antagonists may be a driving factor for its contribution to viral proliferation. We also found that PRRSV infection enhanced DDX21 expression and promoted its nucleus-to-cytoplasm translocation. Screening PRRSV-encoded proteins showed that nsp1β interacted with the C-terminus of DDX21 and enhanced the expression of DDX21. Taken together, these findings reveal that DDX21 plays an important role in regulating PRRSV proliferation through multiple mechanisms.
猪繁殖与呼吸综合征病毒（PRRSV）仍然是全球养猪业的持续威胁。解旋酶 21（DDX21）是 DEAD（Glu-Asp-Ala-Glu）盒家族的一员。除了调节细胞 RNA 代谢的功能外，DDX21 还调节先天免疫，并参与某些病毒的复制周期。然而，DDX21 与 PRRSV 之间的关系尚未得到探索。在这里，我们发现 DDX21 的过表达促进了 PRRSV 的复制，而 DDX21 的敲低则减少了 PRRSV 的增殖。从机制上讲，DDX21 促进 PRRSV 复制不依赖于其 ATP 酶、RNA 解旋酶和折叠酶活性。此外，DDX21 的过表达稳定了 PRRSV nsp1α、nsp1β 和核衣壳蛋白的表达，这三种蛋白是干扰素 β（IFN-β）的已知拮抗剂。DDX21 的敲低激活了 PRRSV 感染细胞中的 IFN-β 信号通路，表明 DDX21 对 PRRSV 编码的 IFN-β 拮抗剂的影响可能是其促进病毒增殖的一个驱动因素。我们还发现 PRRSV 感染增强了 DDX21 的表达并促进了其核质易位。对 PRRSV 编码蛋白的筛选表明，nsp1β 与 DDX21 的 C 端相互作用并增强了 DDX21 的表达。总之，这些发现揭示了 DDX21 通过多种机制在调节 PRRSV 增殖中发挥重要作用。
