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

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.

Figure 1

Graphical summary of the IFN-associated targets and viral evasion molecules employed by HCMV.