Transfection of single-stranded hepatitis A virus RNA activates MHC class I pathway.
Although infection of single-stranded RNA viruses can enhance expression of major histocompatibility complex (MHC) class I genes, the mechanism underlying this process remains unclear. Recent studies have indicated that exposure of non-immune cells to double-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of viral origin can directly increase the expression of MHC class I and related molecules without immune cell interaction. In this report, we show that transfection of single-stranded hepatitis A virus RNA into cultured hepatocytes results in the induction of genes for MHC class I, LMP2 and transporter for antigen processing (TAP1), in addition to the generation of viral proteins. We suggest that this stimulatory effect is due to the double-stranded RNA formed during replication of single-stranded viral RNA, and involves both double-stranded, RNA-dependent protein kinase PKR and the secretion of IFNbeta.
Suzuki
K
K
Cell Regulation Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Maryland, USA. koichis@nih.go.jp
Yanagi
M
M
Mori-Aoki
A
A
Moriyama
E
E
Ishii
K J
KJ
Kohn
L D
LD
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005805:Genes, MHC Class I; D030041:Hepatitis A virus / Q000235:genetics* / Q000502:physiology; D018197:Hepatoblastoma / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D020672:I-kappa B Proteins; D016899:Interferon-beta / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012330:RNA, Double-Stranded / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000502:physiology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015395:Histocompatibility Antigens Class I; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D012367:RNA, Viral; C073119:TAP1 protein, human; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D016899:Interferon-beta; D019892:eIF-2 Kinase