Expression of the interferon-alpha/beta-inducible MxA protein in brain lesions of subacute sclerosing panencephalitis.
The type-I interferon (IFN) inducible human MxA protein exhibits antiviral activity against a variety of RNA viruses including the measles virus (MV). In this study, we investigated the association between the expression of MV antigens and MxA in subacute sclerosing panencephalitis (SSPE) brains. We analyzed the MxA expression in and around lesions in brains of three SSPE patients and compared it with normal brains. Double staining with antibodies against MxA and the MV nucleocapsid revealed that MxA was highly expressed in a belt surrounding MV-antigen-positive lesions in SSPE brains. In normal appearing regions distant from a lesion in SSPE brains and in normal brains, MxA was not detected. Furthermore, MxA was often less or not expressed in the center of lesions expressing high amounts of MV antigens. Such a pattern of MxA expression in SSPE brains clearly indicates that newly infected cells release type I IFN and will become demarcated by a protecting barrier of MxA expressing cells. Double staining with antibodies against MxA and glial fibrillary acidic protein (GFAP) showed that the MxA protein was expressed mainly in the cytoplasm of astrocytes. MxA expression did not correlate with the presence of cellular infiltrates of inflammatory cells, although some lymphoid cells were also positive for MxA. Since MxA inhibits the replication of MV, these findings suggest that the IFN-induced MxA protein plays an important role in slowing down the viral spread in SSPE brains and by doing so may contribute to the persistence of the MV-infection.
Ogata
Seiko
S
Institut für Virologie und Immunbiologie, Versbacher Strasse. 7, D-97078 Würzburg, Germany.
Ogata
Akihiko
A
Schneider-Schaulies
Sibylle
S
Schneider-Schaulies
Sybille
S
Schneider-Schaulies
Jürgen
J
D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000821:virology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016898:Interferon-alpha / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D019251:Nucleocapsid / Q000378:metabolism; D013344:Subacute Sclerosing Panencephalitis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D014764:Viral Proteins; D019204:GTP-Binding Proteins