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

J Med Virol. 2017 Jun;89(6):1069-1079. doi: 10.1002/jmv.24728. Epub 2016 Dec 9.

Abstract

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.

Keywords: HSV-1; MALT1; antiviral signaling pathway; miR-649.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspases
  • HeLa Cells
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Immune Evasion
  • MicroRNAs / metabolism*
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • NF-kappa B / metabolism
  • Neoplasm Proteins / antagonists & inhibitors*
  • Virus Replication*

Substances

  • MIRN649 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Neoplasm Proteins
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein