ABSTRACT
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.
Subject(s)
Gene Expression Regulation, Viral , Genes, MHC Class I , Hepatitis A virus/genetics , Hepatocytes/immunology , Histocompatibility Antigens Class I/biosynthesis , I-kappa B Proteins , RNA, Viral/physiology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP-Binding Cassette Transporters/biosynthesis , ATP-Binding Cassette Transporters/genetics , Cells, Cultured/immunology , DNA-Binding Proteins/metabolism , Hepatitis A virus/physiology , Hepatoblastoma/pathology , Humans , Interferon-beta/metabolism , Liver Neoplasms/pathology , NF-kappa B/metabolism , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Phosphorylation , Protein Processing, Post-Translational , RNA, Double-Stranded/genetics , RNA, Double-Stranded/physiology , RNA, Messenger/biosynthesis , RNA, Viral/genetics , Transfection , Tumor Cells, Cultured/immunology , Viral Matrix Proteins/biosynthesis , Viral Matrix Proteins/genetics , Viral Proteins/biosynthesis , Viral Proteins/genetics , Virus Replication , eIF-2 Kinase/physiologyABSTRACT
Class II transactivator (CIITA) is the master regulator of MHC class II genes, and mediates their induction by interferon gamma (IFN gamma). To study the role of CIITA in modulating the expression of thyroid-specific genes, we cloned the full-length rat CIITA and use it to transfect a rat thyroid cell line. We found that only one type of CIITA, type IV, is induced in thyroid cells upon IFN gamma stimulation, and that CIITA is capable not only of inducing the expression of MHC genes in the thyroid, but also of differentially suppressing the expression of thyroid-specific genes. These findings suggest new avenues for the development of thyroid autoimmune diseases.
