SPONTANEOUS AND DIFFERENTIATION-DEPENDENT REGULATION OF MEASLES-VIRUSGENE-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 ana lyzed. Although all cell lines were permissive for productive replicat ion of all MV strains tested, U-251, D-54, and D-32 cells spontaneousl y revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differenti ation of D-54 and U-251 cells by substances affecting the intracellula r cyclic AMP level caused a significant reduction of the expression of the viral proteins after 18, 72, and 144 h of infection. This pronoun ced restriction was not paralleled to a comparable level by an inhibit ion of the synthesis and biological activity in vitro of virus-specifi c mRNAs as shown by quantitative Northern (RNA) blot analyses and in v itro translation. The block in viral protein synthesis could not be at tributed to the induction of type I interferon by any of the substance s tested. Our findings indicate that down-regulation of MV gene expres sion in human brain cells can occur by a cell type-dependent regulatio n of the viral mRNA transcription and a differentiation-dependent regu lation of translation, both of which may be crucial for the establishm ent of persistent MV infections in the central nervous system.