Differential up-regulation of HLA class I molecules on neuronal and glial cell lines by virus infection correlates with differential induction of IFN-beta.
Adult neurons normally lack the expression of MHC class I molecules, which has implications on virus clearance from the central nervous system. The author previously demonstrated that HLA class I up-regulation in measles virus (MV)-infected glial cells is primarily mediated by IFN-beta. In contrast, this study demonstrates that MV-infection of the neuronal cell lines IMR-32 and CHP-126 fails to up-regulate HLA class I expression, which was associated with an inability of MV to induce IFN-beta in the neuronal cell lines. However, treatment with IFN-beta on coculture of the IMR-32 neuronal cell line with MV-infected glioma cells resulted in the up-regulation of HLA class I on the former, which could be neutralized by anti-IFN-beta Ab. The inability of MV to up-regulate HLA class I expression on the neuronal cell line IMR-32 was not virus specific because similar findings were observed with mumps virus or stimulation with the synthetic dsRNA polyinosinic polycytidylic acid (PIPC). Induction of IFN-beta gene expression by virus requires binding of NF-kappa B to the positive regulatory domain II element of the IFN-beta promoter. Our studies indicate that MV, TNF-alpha, or PIPC induces NF-kappa B (p50 and p65 subunits) binding to positive regulatory domain II in the glioma cell line. In contrast, such activity was induced by TNF-alpha but not MV or PIPC in the neuronal cell line IMR-32. This indicated that HLA class I expression is differentially regulated in glial and neuronal cell lines in response to MV, which correlates with differential binding of NF-kappa B to the IFN-beta promoter and induction of IFN-beta gene expression.
Dhib-Jalbut
S S
SS
Department of Neurology, University of Maryland at Baltimore 21201, USA.
Xia
Q
Q
Drew
P D
PD
Swoveland
P T
PT
D001483:Base Sequence; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D008459:Measles virus / Q000502:physiology*; D008969:Molecular Sequence Data; D009109:Mumps virus / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology*; D009474:Neurons / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D012333:RNA, Messenger; D016899:Interferon-beta; D011070:Poly I-C