Viral Macrodomains: Unique Mediators of Viral Replication and Pathogenesis

Trends Microbiol. 2018 Jul;26(7):598-610. doi: 10.1016/j.tim.2017.11.011.


Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families ​all contain genes that encode a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.

Keywords: ADP-ribosylation; Coronaviridae; Hepeviridae; Togaviridae; interferon (IFN); macrodomain; pathogenesis; poly-ADP-ribose polymerase (PARP); replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Coronaviridae / genetics
  • Coronaviridae / pathogenicity
  • Hepevirus / genetics
  • Hepevirus / pathogenicity
  • Histones
  • Poly(ADP-ribose) Polymerases
  • Protein Domains*
  • Protein Processing, Post-Translational
  • Togaviridae / genetics
  • Togaviridae / pathogenicity
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication*
  • Viruses / enzymology
  • Viruses / genetics*
  • Viruses / pathogenicity*


  • Histones
  • Viral Nonstructural Proteins
  • macroH2A histone
  • Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases