RNA helicase DDX3: at the crossroad of viral replication and antiviral immunity

Rev Med Virol. 2015 Sep;25(5):286-99. doi: 10.1002/rmv.1845. Epub 2015 Jul 14.

Abstract

Asp-Glu-Ala-Asp (DEAD)-box polypeptide 3, or DDX3, belongs to the DEAD-box family of ATP-dependent RNA helicases and is known to play different roles in RNA metabolism ranging from transcription to nuclear export, translation, and assembly of stress granules. In addition, there is growing evidence that DDX3 is a component of the innate immune response against viral infections. As such, DDX3 has been shown to play roles both upstream and downstream of I-kappa beta kinase ε (IKKε)/TANK-binding kinase 1, leading to IFN-β production. Interestingly, several RNA viruses, including human threats such as HIV-1 and hepatitis C virus, hijack DDX3 to accomplish various steps of their replication cycles. Thus, it seems that viruses have evolved to exploit DDX3's functions while threatening the innate immune response. Understanding this interesting dichotomy in DDX3 function will help us not only to improve our knowledge of virus-host interactions but also to develop novel antiviral drugs targeting the multifaceted roles of DDX3 in viral replication.

Publication types

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

MeSH terms

  • DEAD-box RNA Helicases / metabolism*
  • Host-Pathogen Interactions*
  • Humans
  • Immunity, Innate
  • Interferon-beta / metabolism*
  • RNA Helicases / metabolism*
  • RNA Viruses / immunology*
  • RNA Viruses / physiology*
  • Virus Replication*

Substances

  • Interferon-beta
  • DDX3X protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases