PMID- 35326435 OWN - NLM STAT- MEDLINE DCOM- 20220412 LR - 20230308 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 11 IP - 6 DP - 2022 Mar 13 TI - Iron Regulatory Protein 1 Inhibits Ferritin Translation Responding to OsHV-1 Infection in Ark Clams, Scapharca Broughtonii. LID - 10.3390/cells11060982 [doi] LID - 982 AB - Elemental iron is an indispensable prosthetic group of DNA replication relative enzymes. The upregulation of ferritin translation by iron regulatory proteins (IRP1) in host cells is a nutritional immune strategy to sequester available iron to pathogens. The efficient replication of Ostreid herpesvirus 1 (OsHV-1), a lethal dsDNA virus among bivalves, depends on available iron. OsHV-1 infection was found to trigger iron limitation in ark clams; however, it is still an enigma how OsHV-1 successfully conducted rapid replication, escaping host iron limitations. In this study, we identified the IRP1 protein (designated as SbIRP-1) in the ark clam (Scapharca broughtonii) and found it could bind to the iron-responsive element (IRE) of ferritin (SbFn) mRNA based on electrophoretic mobility shift assay (EMSA). Knockdown of SbIRP-1 expression (0.24 +/- 1.82-fold of that in NC group, p < 0.01) by RNA interference resulted in the accumulation of SbFn in hemocytes (1.79 +/- 0.01-fold, p < 0.01) post-24 h of enhanced RNA interference injection. During OsHV-1 infection, SbFn mRNA was significantly upregulated in hemocytes from 24 h to 60 h, while its protein level was significantly reduced from 24 h to 48 h, with the lowest value at 36 h post-infection (0.11 +/- 0.01-fold, p < 0.01). Further analysis by RNA immunoprecipitation assays showed that OsHV-1 could enhance the binding of SbIRP-1 with the SbFn IRE, which was significantly increased (2.17 +/- 0.25-fold, p < 0.01) at 36 h post-infection. Consistently, SbIRP-1 protein expression was significantly increased in hemocytes from 12 h to 48 h post OsHV-1 infection (p < 0.01). In conclusion, the results suggest that OsHV-1 infection could suppress post-transcriptional translation of SbFn through the regulation of SbIRP-1, which likely contributes to OsHV-1 evasion of SbFn-mediating host iron limitation. FAU - Huang, Bowen AU - Huang B AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. FAU - Zhang, Xiang AU - Zhang X AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. FAU - Liu, Qin AU - Liu Q AUID- ORCID: 0000-0002-2549-3425 AD - Guangxi Key Laboratory for Agricultural Resources Chemistry and Biotechnology, College of Biology and Pharmacy, Yulin Normal University, Yulin 537000, China. FAU - Bai, Changming AU - Bai C AUID- ORCID: 0000-0001-5476-2455 AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. FAU - Li, Chen AU - Li C AUID- ORCID: 0000-0002-2862-5702 AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. FAU - Wang, Chongming AU - Wang C AUID- ORCID: 0000-0002-5517-9453 AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. FAU - Xin, Lusheng AU - Xin L AUID- ORCID: 0000-0002-4685-1076 AD - Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China. AD - Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. LA - eng GR - 31902400/National Natural Science Foundation of China/ GR - 20603022020007/the Special Scientific Research Funds for Central Non-profit Institutes, Yellow Sea Fisheries Research Institutes/ GR - CARS49/China Agriculture Research System of MOF and MARA/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220313 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (RNA, Messenger) RN - 9007-73-2 (Ferritins) RN - E1UOL152H7 (Iron) RN - EC 4.2.1.3 (Iron Regulatory Protein 1) SB - IM MH - Animals MH - Ferritins/genetics/metabolism MH - Iron/metabolism MH - Iron Regulatory Protein 1/metabolism MH - RNA, Messenger/genetics MH - *Scapharca/genetics PMC - PMC8947174 OTO - NOTNLM OT - OsHV-1 OT - Scapharca broughtonii OT - ferritin OT - iron metabolism OT - iron regulatory protein 1 COIS- The authors declare no conflict of interest. EDAT- 2022/03/26 06:00 MHDA- 2022/04/13 06:00 PMCR- 2022/03/13 CRDT- 2022/03/25 01:01 PHST- 2022/02/16 00:00 [received] PHST- 2022/03/11 00:00 [revised] PHST- 2022/03/11 00:00 [accepted] PHST- 2022/03/25 01:01 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/04/13 06:00 [medline] PHST- 2022/03/13 00:00 [pmc-release] AID - cells11060982 [pii] AID - cells-11-00982 [pii] AID - 10.3390/cells11060982 [doi] PST - epublish SO - Cells. 2022 Mar 13;11(6):982. doi: 10.3390/cells11060982.