The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus

J Mol Biol. 2013 Dec 13;425(24):4857-71. doi: 10.1016/j.jmb.2013.08.023. Epub 2013 Sep 5.

Abstract

Human cytomegalovirus (HCMV) is a member of the β-herpesvirus family that invariably occupies hosts for life despite a consistent multi-pronged antiviral immune response that targets the infection. This persistence is enabled by the large viral genome that encodes factors conferring a wide assortment of sophisticated, often redundant phenotypes that disable or otherwise manipulate impactful immune effector processes. The type I interferon system represents a first line of host defense against infecting viruses. The physiological reactions induced by secreted interferon act to effectively block replication of a broad spectrum of virus types, including HCMV. As such, the virus must exhibit counteractive mechanisms to these responses that involve their inhibition, tolerance, or re-purposing. The goal of this review is to describe the impact of the type I interferon system on HCMV replication and to showcase the number and diversity of strategies employed by the virus that allow infection of hosts in the presence of interferon-dependent activity.

Keywords: COX2; HCMV; HIV; HSV; Herpes Simplex virus; IFI16; IFN promoter stimulator 1; IFN regulatory factor; IFN-stimulated gene; IFNγ-inducible protein 16; IPS1; IRF; ISG; MCMV; NFκB; NK; ORF; PKR; PML; PRR; RIG-I; cyclooxygenase 2; cytomegalovirus; double-stranded DNA; double-stranded RNA; dsDNA; dsRNA; human cytomegalovirus; human immunodeficiency virus; immune evasion; innate immunity; interferon; murine cytomegalovirus; natural killer; nuclear factor κB; open reading frame; pattern recognition receptor; promyelocytic leukemia; protein kinase R; retinoic acid-inducible gene I.

Publication types

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

MeSH terms

  • Cytomegalovirus / immunology*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immune Evasion
  • Immunity, Innate
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Interferon Type I / metabolism
  • Models, Molecular
  • Signal Transduction
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Proteins / metabolism
  • Virulence Factors / genetics
  • Virulence Factors / immunology
  • Virulence Factors / metabolism
  • Virus Replication

Substances

  • Interferon Type I
  • Viral Proteins
  • Virulence Factors