PMID- 35336874 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220531 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 14 IP - 3 DP - 2022 Feb 24 TI - DEAD-Box RNA Helicase 21 (DDX21) Positively Regulates the Replication of Porcine Reproductive and Respiratory Syndrome Virus via Multiple Mechanisms. LID - 10.3390/v14030467 [doi] LID - 467 AB - 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 nsp1alpha, nsp1beta, and nucleocapsid proteins, three known antagonists of interferon beta (IFN-beta). Knockdown of DDX21 activated the IFN-beta signaling pathway in PRRSV-infected cells, suggesting that the effect of DDX21 on PRRSV-encoded IFN-beta 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 nsp1beta 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. FAU - Li, Jia AU - Li J AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Wang, Dang AU - Wang D AUID- ORCID: 0000-0003-3394-3702 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Fang, Puxian AU - Fang P AUID- ORCID: 0000-0002-0539-8578 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Pang, Yu AU - Pang Y AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Zhou, Yanrong AU - Zhou Y AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Fang, Liurong AU - Fang L AUID- ORCID: 0000-0003-1406-6409 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Xiao, Shaobo AU - Xiao S AUID- ORCID: 0000-0003-0023-9188 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220224 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Viral Nonstructural Proteins) RN - 77238-31-4 (Interferon-beta) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Animals MH - Cell Line MH - DEAD-box RNA Helicases/genetics/metabolism MH - Interferon-beta/genetics MH - *Porcine Reproductive and Respiratory Syndrome/genetics MH - *Porcine respiratory and reproductive syndrome virus/metabolism MH - Swine MH - Viral Nonstructural Proteins/genetics/metabolism MH - Virus Replication/physiology PMC - PMC8949431 OTO - NOTNLM OT - DEAD-box helicases 21 (DDX21) OT - interaction OT - interferon OT - nonstructural protein 1beta (nsp1beta) OT - porcine reproductive and respiratory syndrome virus (PRRSV) OT - viral replication COIS- The authors declare no conflict of interest. EDAT- 2022/03/27 06:00 MHDA- 2022/04/15 06:00 PMCR- 2022/02/24 CRDT- 2022/03/26 01:07 PHST- 2022/02/12 00:00 [received] PHST- 2022/02/21 00:00 [revised] PHST- 2022/02/23 00:00 [accepted] PHST- 2022/03/26 01:07 [entrez] PHST- 2022/03/27 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2022/02/24 00:00 [pmc-release] AID - v14030467 [pii] AID - viruses-14-00467 [pii] AID - 10.3390/v14030467 [doi] PST - epublish SO - Viruses. 2022 Feb 24;14(3):467. doi: 10.3390/v14030467.