RECEPTOR (CD46)-MEDIATED AND REPLICATION-MEDIATED INTERLEUKIN-6 INDUCTION BY MEASLES-VIRUS IN HUMAN ASTROCYTOMA-CELLS

A major source of inflammatory cytokines in the measles virus (MV)-inf ected brain are astrocytes, which produce a variety of soluble mediato rs including interferons-alpha/beta (IFN-alpha/beta), interleukin-1 (I L-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6 ). Using the MV-strain Edmonston (ED) and the recombinant MV-strain MG V in which the MV-envelope proteins H and F have been replaced by the vesicular stomatitis virus (VSV) envelope protein G, we investigated I L-6 induction in human U-251 astrocytoma cells in the presence and abs ence of a MV-specific receptor (CD46) interaction. The CD46-MV interac tion did not inhibit the induction of cytokines, Similar multiplicitie s of infection of MGV induced generally lower levels of IL-6 than MV-E D, UV-inactivated replication-incompetent MV-ED induced low levels of IL-6, In contrast, MGV did not induce IL-6 after inactivation with UV light, indicating that the MV-ED-receptor interaction or the uptake of viral particles by membrane fusion induced IL-6, whereas interaction with the VSV-G receptor and uptake of viral particles by endocytosis d id not induce IL-6, Crosslink of the MV-receptor CD46 with antibodies and treatment of cells with purified viral glycoproteins led to the in duction of small but significant amounts of IL-6, Our data suggest tha t triggering of CD46 and associated protein kinases can lead to the in duction of low levels of IL-6, whereas the replication of the negative strand RNA virus constitutes the major stimulus leading to the synthe sis of high levels of IL-6 in astrocytes.