The Tiers and Dimensions of Evasion of the Type I Interferon Response by Human Cytomegalovirus

• Published in: Journal of molecular biology 2013-12, Vol.425 (24), p.4857-4871
• Main Authors: Amsler, Lisi, Verweij, Marieke C., DeFilippis, Victor R.
• Format: Article
• Language: English
• Subjects: cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus - physiology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; genome; Host-Pathogen Interactions - immunology; hosts; Human cytomegalovirus; Human herpesvirus 5; Humans; Immune Evasion; immune response; Immunity, Innate; innate immunity; interferon; Interferon Type I - genetics; Interferon Type I - immunology; Interferon Type I - metabolism; interferons; Models, Molecular; phenotype; Signal Transduction; Viral Proteins - genetics; Viral Proteins - immunology; Viral Proteins - metabolism; Virulence Factors - genetics; Virulence Factors - immunology; Virulence Factors - metabolism; Virus Replication; viruses
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2013.08.023

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. [Display omitted] •Human cytomegalovirus is an extremely immunogenic pathogen that infects hosts for life.•Lifelong infection requires numerous sophisticated mechanisms of immune evasion.•The type I interferon system represents the first line of defense against a broad array of virus types including cytomegalovirus.•Human cytomegalovirus has evolved multiple phenotypes to counteract, withstand, or co-opt physiological responses induced by type I interferons.