MicroRNA-649 promotes HSV-1 replication by directly targeting MALT1

Herpes simplex virus type 1 (HSV-1), a member of the Herpes viridae, is associated with a wide variety of nervous system diseases including meningitis and encephalitis. The data presented here demonstrate that miR-649 promotes the replication of HSV-1 without affecting cell viability. Further mechanistic studies revealed that MALT1 (mucosa associated lymphoid tissue lymphoma translocation gene 1) is directly targeted by miR-649. We then found that MALT1 and the downstream NF-κB signaling pathway, are involved in miR-649-induced HSV-1 replication. Interestingly, miR-649 levels were downregulated after HSV-1 infection, and miR-649 expression was negatively associated with MALT1 expression in HSV-1-infected HeLa cells. Taken together, this present study indicates that miR-649 promotes HSV-1 replication through regulation of the MALT1-mediated antiviral signaling pathway and suggests a promising target for antiviral therapies. J. Med. Virol. 89:1069-1079, 2017. © 2016 Wiley Periodicals, Inc.