CELL-TYPE-SPECIFIC MXA-MEDIATED INHIBITION OF MEASLES-VIRUS TRANSCRIPTION IN HUMAN BRAIN-CELLS

Measles virus (MV)-specific transcription in human brain cells is char acterized by particularly low abundances of the distal mRNAs encoding the MV envelope proteins. Similar transcriptional restrictions of the closely related vesicular stomatitis virus have been observed in mouse fibroblasts constitutively expressing the interferon-inducible MxA pr otein (P. Staeheli and J. Pavlovic, J. Virol. 65:4498-4501, 1991). We found that MV infection of human brain cells is accompanied by rapid i nduction and high-level expression of endogenous MxA proteins. After s table transfection of MxA, human glioblastoma cells (U-87-MxA) release d 50- to 100-fold less infectious virus and expression of viral protei ns was highly restricted. The overall MV-specific transcription levels were reduced by up to 90%, accompanied by low relative frequencies of the distal MV-specific mRNAs. These restrictions were linked to an in hibition of viral RNA synthesis and not to a decreased stability of th e viral RNAs. Our results indicate that expression of MxA is associate d with transcriptional attenuation of MV in brain cells, thus probably contributing to the establishment of persistent MV central nervous sy stem infections. In addition, the mechanism of MxA-dependent resistanc e against MV infection, in contrast to that of vesicular stomatitis vi rus, is cell type specific, because an inhibition of MV glycoprotein s ynthesis independent of transcriptional alterations was observed in Mx A-transfected human monocytes (J.-J. Schnorr, S. Schneider-Schaulies, A. Simon-Jodicke, J. Pavlovic, M. A. Horisberger, and V. ter Meulen, J . Virol. 67: 4760-4768, 1993).