Open Accesspol-miR-731, a teleost miRNA upregulated by megalocytivirus, negatively regulates virus-induced type I interferon response, apoptosis and cell cycle arrest
Author(s) -
Baocun Zhang,
Zejun Zhou,
Li Sun
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep28354
Subject(s) - olive flounder , irf7 , biology , interferon , interferon regulatory factors , virology , viral replication , virus , apoptosis , microbiology and biotechnology , irf1 , microrna , gene , gene expression , genetics , transcription factor , fishery , fish <actinopterygii>
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.