The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation

Viruses. 2020 Mar 31;12(4):384. doi: 10.3390/v12040384.


Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein-protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, implicating ADP-ribosylation in the host defense response and suggesting that viral macrodomains may counter this response. Recent studies have demonstrated that viral macrodomains do counter the innate immune response by interfering with PARP-mediated antiviral defenses, stress granule formation, and pro-inflammatory cytokine production. Here, we will describe the known functions of the viral macrodomains and review recent literature demonstrating their roles in countering PARP-mediated antiviral responses.

Keywords: ADP-ribose; ADP-ribosylation; PARPs; RNA virus; alphaviruses; coronaviruses; hepatitis E virus; macrodomain; stress granule.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ADP-Ribosylation / immunology*
  • Adenosine Diphosphate Ribose / metabolism
  • Cytoplasmic Granules / immunology
  • Cytoplasmic Granules / virology
  • Humans
  • Interferons / immunology
  • Mutation
  • Poly(ADP-ribose) Polymerases / immunology
  • Protein Domains
  • RNA Virus Infections / immunology
  • RNA Virus Infections / metabolism
  • RNA Virus Infections / virology
  • RNA Viruses / classification
  • RNA Viruses / genetics
  • RNA Viruses / immunology*
  • RNA Viruses / metabolism
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication


  • Viral Nonstructural Proteins
  • Adenosine Diphosphate Ribose
  • Interferons
  • Poly(ADP-ribose) Polymerases