RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections

Madalina E Carter-Timofte; Søren R Paludan; Trine H Mogensen

doi:10.1016/j.molmed.2018.07.009

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.

Authors

Madalina E Carter-Timofte¹, Søren R Paludan², Trine H Mogensen³

Affiliations

¹ Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark.
² Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark; Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark; Department of Clinical Medicine, Aarhus University, Palle Juul Jensens Boulevard 82, 8200 Aarhus N, Denmark. Electronic address: trine.mogensen@biomed.au.dk.

PMID: 30115567
DOI: 10.1016/j.molmed.2018.07.009

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
Receptors, Immunologic
Virus Activation*

Substances

DNA, Viral
Protein Subunits
Receptors, Immunologic
Interferons
RNA Polymerase III
RIGI protein, human
DEAD Box Protein 58