RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections

Trends Mol Med. 2018 Oct;24(10):904-915. doi: 10.1016/j.molmed.2018.07.009. Epub 2018 Aug 13.

Abstract

In most individuals, varicella zoster virus (VZV) causes varicella upon primary infection and zoster during reactivation. However, in a subset of individuals, VZV may cause severe disease, including encephalitis. Host genetics is believed to be the main determinant of exacerbated disease manifestations. Recent studies have demonstrated that defects in the DNA sensor RNA polymerase III (POL III) confer selective increased susceptibility to VZV infection, thus providing fundamental new insight into VZV immunity. Here we describe the roles of POL III in housekeeping and immune surveillance during VZV infection. We present the latest knowledge on the role of POL III in VZV infection and discuss outstanding questions related to the role of POL III in VZV immunity, and how this insight can be translated into clinical medicine.

Keywords: DNA sensing; RNA polymerase III; interferon; varicella zoster virus.

Publication types

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

MeSH terms

  • Adult
  • Chickenpox / genetics*
  • Chickenpox / immunology
  • Chickenpox / pathology
  • Chickenpox / virology
  • DEAD Box Protein 58 / genetics
  • DEAD Box Protein 58 / immunology
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Encephalitis, Varicella Zoster / genetics*
  • Encephalitis, Varicella Zoster / immunology
  • Encephalitis, Varicella Zoster / pathology
  • Encephalitis, Varicella Zoster / virology
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Herpes Zoster / genetics*
  • Herpes Zoster / immunology
  • Herpes Zoster / pathology
  • Herpes Zoster / virology
  • Herpesvirus 3, Human / genetics
  • Herpesvirus 3, Human / immunology
  • Host-Pathogen Interactions*
  • Humans
  • Immunity, Innate
  • Immunologic Surveillance
  • Interferons / genetics
  • Interferons / immunology
  • Protein Subunits / genetics
  • Protein Subunits / immunology
  • RNA Polymerase III / genetics*
  • RNA Polymerase III / immunology
  • Virus Activation*

Substances

  • DNA, Viral
  • Protein Subunits
  • Interferons
  • RNA Polymerase III
  • DDX58 protein, human
  • DEAD Box Protein 58