Receptor (CD46)- and replication-mediated interleukin-6 induction by measles virus in human astrocytoma cells.
A major source of inflammatory cytokines in the measles virus (MV)-infected brain are astrocytes, which produce a variety of soluble mediators including interferons-alpha/beta (IFN-alpha/beta), interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Using the MV-strain Edmonston (ED) and the recombinant MV-strain MGV in which the MV-envelope proteins H and F have been replaced by the vesicular stomatitis virus (VSV) envelope protein G, we investigated IL-6 induction in human U-251 astrocytoma cells in the presence and absence of a MV-specific receptor (CD46) interaction. The CD46-MV interaction did not inhibit the induction of cytokines. Similar multiplicities of infection of MGV induced generally lower levels of IL-6 than MV-ED. 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 did not induce IL-6. Crosslink of the MV-receptor CD46 with antibodies and treatment of cells with purified viral glycoproteins led to the induction of small but significant amounts of IL-6. Our data suggest that triggering of CD46 and associated protein kinases can lead to the induction of low levels of IL-6, whereas the replication of the negative strand RNA virus constitutes the major stimulus leading to the synthesis of high levels of IL-6 in astrocytes.
Ghali
M
M
Institut für Virologie und Immunbiologie, Würzburg, Germany.
Schneider-Schaulies
J
J
D015703:Antigens, CD / Q000502:physiology*; D001253:Astrocytes / Q000276:immunology / Q000821:virology*; D001254:Astrocytoma; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008459:Measles virus / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D011070:Poly I-C / Q000494:pharmacology; D011940:Receptor Aggregation; D011991:Receptors, Virus / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
D015703:Antigens, CD; C497857:CD46 protein, human; D002352:Carrier Proteins; C028391:G protein, vesicular stomatitis virus; D006389:Hemagglutinins, Viral; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus; C015482:protein kinase modulator; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D011070:Poly I-C