pol-miR-731, a teleost miRNA upregulated by megalocytivirus, negatively regulates virus-induced type I interferon response, apoptosis and cell cycle arrest

• DOI: 10.1038/srep28354
• Publication Date: 2016-06-17T09:42:58Z
• Authors: Bao-cun Zhang; Ze-jun Zhou; Li Sun
• Keywords: Fish Proteins; 0303 health sciences; Interferon Regulatory Factor-7; Apoptosis; Cell Cycle Checkpoints; Flounder; Virus Replication; Article; Iridoviridae; 3. Good health; MicroRNAs; 03 medical and health sciences; Host-Pathogen Interactions; Interferon Type I; Animals; RNA, Viral; 14. Life underwater; Tumor Suppressor Protein p53

AbstractMegalocytivirus 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.