pol-miR-731, a teleost miRNA upregulated by megalocytivirus, negatively regulates virus-induced type I interferon response, apoptosis, and cell cycle arrest.
Megalocytivirus is a DNA virus that is highly infectious in a wide variety of marine and freshwater fish, including Japanese flounder (Paralichthys olivaceus), a flatfish that is farmed worldwide. However, the infection mechanism of megalocytivirus remains largely unknown. In this study, we investigated the function of a flounder microRNA, pol-miR-731, in virus-host interaction. We found that pol-miR-731 was induced in expression by megalocytivirus and promoted viral replication at the early infection stage. In vivo and in vitro studies revealed that pol-miR-731 (i) specifically suppresses the expression of interferon regulatory factor 7 (IRF7) and cellular tumor antigen p53 in a manner that depended on the integrity of the pol-miR-731 complementary sequences in the 3' untranslated regions of IRF7 and p53, (ii) disrupts megalocytivirus-induced Type I interferon response through IRF7, (iii) inhibits megalocytivirus-induced splenocyte apoptosis and cell cycle arrest through p53. Furthermore, overexpression of IRF7 and p53 abolished both the inhibitory effects of pol-miR-731 on these biological processes and its stimulatory effect on viral replication. These results disclosed a novel evasion mechanism of megalocytivirus mediated by a host miRNA. This study also provides the first evidence that a virus-induced host miRNA can facilitate viral infection by simultaneously suppressing several antiviral pathways.
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.|Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Bao-Cun
BC
Zhang
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.|Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.|University of Chinese Academy of Sciences, Beijing, China.
Ze-Jun
ZJ
Zhou
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.|Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Li
L
Sun
D000818:Animals; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D029941:Fish Proteins / Q000235:genetics; D005432:Flounder / Q000235:genetics / Q000276:immunology / Q000821:virology*; D054884:Host-Pathogen Interactions; D050839:Interferon Regulatory Factor-7 / Q000235:genetics*; D007370:Interferon Type I / Q000235:genetics; D007497:Iridoviridae / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014779:Virus Replication
D029941:Fish Proteins; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D035683:MicroRNAs; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53