Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells.
The expression of measles virus (MV) in six different permanent human glioma cell lines (D-54, U-251, U-138, U-105, U-373, and D-32) was analyzed. Although all cell lines were permissive for productive replication of all MV strains tested, U-251, D-54, and D-32 cells spontaneously revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differentiation of D-54 and U-251 cells by substances affecting the intracellular cyclic AMP level caused a significant reduction of the expression of the viral proteins after 18, 72, and 144 h of infection. This pronounced restriction was not paralleled to a comparable level by an inhibition of the synthesis and biological activity in vitro of virus-specific mRNAs as shown by quantitative Northern (RNA) blot analyses and in vitro translation. The block in viral protein synthesis could not be attributed to the induction of type I interferon by any of the substances tested. Our findings indicate that down-regulation of MV gene expression in human brain cells can occur by a cell type-dependent regulation of the viral mRNA transcription and a differentiation-dependent regulation of translation, both of which may be crucial for the establishment of persistent MV infections in the central nervous system.
Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
S
S
Schneider-Schaulies
J
J
Schneider-Schaulies
M
M
Bayer
S
S
Löffler
V
V
ter Meulen
D002454:Cell Differentiation; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics*; D007370:Interferon Type I / Q000096:biosynthesis; D008459:Measles virus / Q000235:genetics* / Q000254:growth & development; D009457:Neuroglia / Q000382:microbiology*; D010208:Papaverine / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication
D007370:Interferon Type I; D012333:RNA, Messenger; D012367:RNA, Viral; D010208:Papaverine; D000242:Cyclic AMP