Human cytomegalovirus inhibition of major histocompatibility complex transcription and interferon signal transduction.
Pathogens have evolved diverse mechanisms for escaping host innate and adaptive immunity. Viruses that maintain a persistent infection are particularly effective at disabling key arms of the host immune response. For example, the herpesviruses establish a persistent infection in human and animal hosts, in part through critical immunoevasive strategies. Cytomegalovirus, a beta-herpesvirus, impairs major histocompatibility complex (MHC) class I and class II antigen presentation by decreasing MHC expression on the surface of the infected cell, thus enabling infected cells to escape CD8+ and CD4+ T lymphocyte immunosurveillance. Moreover, cytomegalovirus blocks the interferon signal transduction pathway, thereby limiting the direct and indirect antiviral effects of the interferons. In this review, we focus on an emerging paradigm in which the effectiveness of viruses, particularly human cytomegalovirus, to escape antiviral immune responses is significantly enhanced by their ability to inhibit MHC transcription and interferon (IFN)-stimulated (JAK/STAT) signal transduction.
Miller
D M
DM
Department of Pathology, Ohio State University College of Medicine, 1645 Neil Avenue, Room 129, Columbus, OH 43210, USA.
Cebulla
C M
CM
Sedmak
D D
DD
D017951:Antigen Presentation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D053613:Janus Kinase 1; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007372:Interferons; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1