Effect of human cytomegalovirus on expression of MHC class I-related chains A.
The MHC-encoded MHC class I-related chains A (MICA) glycoproteins are known to enhance the functions of NK and T cells by ligating the stimulating receptor NKG2D and appear to play an important role in host defense. Human CMV (HCMV) evades the immune response in many different ways, but has not previously been found to down-regulate MICA. We have found that a common form of MICA, which has a nucleotide insertion in exon 5 corresponding to the transmembrane region and no cytoplasmic tail, was increased on the surface of fibroblasts HFS-13 compared with the mock-infected sample of the same cells that had been cultured to confluence. However, an astrocytoma cell line, U373, which has a full-length variant of MICA, showed that the expression of MICA was decreased after HCMV infection. Retroviral transduction of different MICA alleles into fibroblasts HFF-D, which express no MICA of their own, established that full-length MICA was down-regulated by HCMV, and the truncated form was not. Fibroblasts with decreased MICA due to HCMV infection were found to be protected from NK cell killing, whereas in the presence of the truncated form of MICA, the virus-infected cells were destroyed. Thus, the truncated form of MICA, which is the most common, has a mutation that allows it to persist on the surface and hinder efforts of the virus to evade the immune response.
Zou
Yizhou
Y
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Bresnahan
Wade
W
Taylor
R Travis
RT
Stastny
Peter
P
D001254:Astrocytoma / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017353:Gene Deletion; D006023:Glycoproteins; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D006023:Glycoproteins; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; C099187:MHC class I-related chain A; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C082590:UL4 protein, Human cytomegalovirus; C074546:US11 protein, herpesvirus; C095111:US3 protein, cytomegalovirus; C432877:US6 protein, Human cytomegalovirus; C456061:US8 protein, Human herpesvirus 5; C456063:US9 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins