title: The MHC class I homolog of human cytomegalovirus is resistant to down-regulation mediated by the unique short region protein (US)2, US3, US6, and US11 gene products.
abstract: Human CMV encodes four unique short region proteins (US), US2, US3, US6, and US11, each independently sufficient for causing the down-regulation of MHC class I molecules on the cell surface. This down-regulation allows infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to NK cells, which lyse cells that lack class I molecules. Another human CMV-encoded protein, unique long region protein 18 (UL18), is an MHC class I homolog that might provide a mechanism for inhibiting the NK cell response. The sequence similarities between MHC class I molecules and UL18 along with the ability of UL18 to form trimeric complexes with beta(2)-microglobulin and peptides led to the hypothesis that if the US and UL18 gene products coexist temporally during infection, the US proteins might down-regulate UL18 molecules, similar to their action on MHC class I molecules. We show here that temporal expression of US and UL18 genes partially overlaps during infection. However, unlike MHC class I molecules, the MHC class I homolog, UL18, is fully resistant to the down-regulation associated with the US2, US3, US6, and US11 gene products. The specific effect of US proteins on MHC class I molecules, but not on UL18, represents another example of how viral proteins have evolved to evade immune surveillance, avoiding fratricide by specifically targeting host proteins.
authors.affiliation: Graduate School of Biotechnology, Korea University, Seoul, Korea.
authors.forename: Boyoun
authors.initials: B
authors.lastname: Park
authors.forename: Hokyung
authors.initials: H
authors.lastname: Oh
authors.forename: Sungwook
authors.initials: S
authors.lastname: Lee
authors.forename: Yangsook
authors.initials: Y
authors.lastname: Song
authors.forename: Jinwook
authors.initials: J
authors.lastname: Shin
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Sue-Yun
authors.initials: SY
authors.lastname: Hwang
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D002213:Capsid / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D036022:Capsid Proteins; D003587:Cytomegalovirus / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D036022:Capsid Proteins; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; C095111:US3 protein, cytomegalovirus; C432877:US6 protein, Human cytomegalovirus; C079750:VP23 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins