title: The HCMV gene products US2 and US11 target MHC class I molecules for degradation in the cytosol.
abstract: Over millions of years of coevolution with their hosts, viruses have developed highly effective strategies to elude the host immune system. The degradation of major histocompatibility complex (MHC) class I heavy chains by human cytomegalovirus (HCMV) is an example of this. Two HCMV proteins, US2 and US11, target newly synthesized MHC class I heavy chains for destruction via a pathway that involves ubiquitin-dependent retrograde transport, or "dislocation", of the heavy chains from the ER to the cytosol, where the proteins are degraded by proteasomes. In this review, US2- and US11-mediated degradation of MHC class I heavy chains is discussed in relation to data concerning the degradation of other ER luminal proteins. A new, unified model for translocon-facilitated dislocation and degradation of MHC class I heavy chains is presented.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van der Wal
authors.forename: M
authors.initials: M
authors.lastname: Kikkert
authors.forename: E
authors.initials: E
authors.lastname: Wiertz
mesh_terms: D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins