Cell-cell fusion induced by measles virus amplifies the type I interferon response.
Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-beta) production is amplified in vitro by the formation of virus-induced MGC derived from human epithelial cells or mature conventional dendritic cells. Both fusion and IFN-beta response amplification were inhibited in a dose-dependent way by a fusion-inhibitory peptide after MeV infection of epithelial cells. This effect was observed at both low and high multiplicities of infection. While in the absence of virus replication, the cell-cell fusion mediated by MeV H/F glycoproteins did not activate any IFN-alpha/beta production, an amplified IFN-beta response was observed when H/F-induced MGC were infected with a nonfusogenic recombinant chimerical virus. Time lapse microscopy studies revealed that MeV-infected MGC from epithelial cells have a highly dynamic behavior and an unexpected long life span. Following cell-cell fusion, both of the RIG-I and IFN-beta gene deficiencies were trans complemented to induce IFN-beta production. Production of IFN-beta and IFN-alpha was also observed in MeV-infected immature dendritic cells (iDC) and mature dendritic cells (mDC). In contrast to iDC, MeV infection of mDC induced MGC, which produced enhanced amounts of IFN-alpha/beta. The amplification of IFN-beta production was associated with a sustained nuclear localization of IFN regulatory factor 3 (IRF-3) in MeV-induced MGC derived from both epithelial cells and mDC, while the IRF-7 up-regulation was poorly sensitive to the fusion process. Therefore, MeV-induced cell-cell fusion amplifies IFN-alpha/beta production in infected cells, and this indicates that MGC contribute to the antiviral immune response.
Herschke
F
F
Interactions Virus Cellule-Hôte, CNRS, Université de Lyon 1, FRE3011, IFR 62 Laennec, 69372 Lyon Cedex 08, France.
Plumet
S
S
Duhen
T
T
Azocar
O
O
Druelle
J
J
Laine
D
D
Wild
T F
TF
Rabourdin-Combe
C
C
Gerlier
D
D
Valentin
H
H
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology*; D015726:Giant Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000032:analysis; D050839:Interferon Regulatory Factor-7 / Q000032:analysis; D007370:Interferon Type I / Q000096:biosynthesis*; D008459:Measles virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D018715:Microscopy, Video; D014760:Viral Fusion Proteins / Q000276:immunology / Q000502:physiology; D014764:Viral Proteins / Q000276:immunology / Q000502:physiology
D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D014760:Viral Fusion Proteins; D014764:Viral Proteins