Dengue Virus Control of Type I IFN Responses: A History of Manipulation and Control

J Interferon Cytokine Res. 2015 Jun;35(6):421-30. doi: 10.1089/jir.2014.0129. Epub 2015 Jan 28.

Abstract

The arthropod-borne diseases caused by dengue virus (DENV) are a major and emerging problem of public health worldwide. Infection with DENV causes a series of clinical manifestations ranging from mild flu syndrome to severe diseases that include hemorrhage and shock. It has been demonstrated that the innate immune response plays a key role in DENV pathogenesis. However, in recent years, it was shown that DENV evades the innate immune response by blocking type I interferon (IFN-I). It has been demonstrated that DENV can inhibit both the production and the signaling of IFN-I. The viral proteins, NS2A and NS3, inhibit IFN-I production by degrading cellular signaling molecules. In addition, the viral proteins, NS2A, NS4A, NS4B, and NS5, can inhibit IFN-I signaling by blocking the phosphorylation of the STAT1 and STAT2 molecules. Finally, NS5 mediates the degradation of STAT2 using the proteasome machinery. In this study, we briefly review the most recent insights regarding the IFN-I response to DENV infection and its implication for pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dengue / genetics
  • Dengue / immunology*
  • Dengue / pathology
  • Dengue / virology
  • Dengue Virus / immunology*
  • Dengue Virus / pathogenicity
  • Gene Expression Regulation
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Innate
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Proteolysis
  • RNA Helicases / genetics
  • RNA Helicases / immunology
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT2 Transcription Factor / genetics
  • STAT2 Transcription Factor / immunology
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology

Substances

  • Interferon Type I
  • NS2A protein, Dengue virus type 2
  • NS3 protein, flavivirus
  • NS4A protein, Dengue virus
  • NS4B protein, flavivirus
  • NS5 protein, dengue virus
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Viral Nonstructural Proteins
  • Serine Endopeptidases
  • RNA Helicases