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Journal of Virology, December 2007, p. 12859-12871, Vol. 81, No. 23
0022-538X/07/$08.00+0 doi:10.1128/JVI.00078-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
,
S. Plumet,1,
T. Duhen,2,
O. Azocar,2
J. Druelle,3
D. Laine,2
T. F. Wild,3
C. Rabourdin-Combe,2,
D. Gerlier,1,
and
H. Valentin2*,
Interactions Virus Cellule-Hôte, CNRS, Université de Lyon 1, FRE3011, IFR 62 Laennec, 69372 Lyon Cedex 08, France,1 Interaction Virus-Système Immunitaire, INSERM, U851, IFR128 BioSciences Lyon—Gerland, Université de Lyon 1, HCL, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France,2 Immunobiologie des Infections Virales, INSERM, U758, IFR128 BioSciences Lyon—Gerland, Université de Lyon 1, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France3
Received 11 January 2007/ Accepted 30 August 2007
Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-ß) 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-ß 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-
/ß production, an amplified IFN-ß 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-ß gene deficiencies were trans complemented to induce IFN-ß production. Production of IFN-ß and IFN-
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-
/ß. The amplification of IFN-ß 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-
/ß production in infected cells, and this indicates that MGC contribute to the antiviral immune response.
Published ahead of print on 26 September 2007.
Supplemental material for this article may be found at http://jvi.asm.org/.
F.H., S.P., and T.D. contributed equally to this work.
C.R.-C, D.G., and H.V. contributed equally to this work.
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