Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses

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  • Ole Jensen Hamming, Danmark
  • Ewa Terczynska-Dyla
  • Gabrielle Vieyres, Institute of Experimental Virology, TWINCORE- Centre for Experimental and Clinical, Infection Research, Hannover, Tyskland
  • Ronald Dijkman, Institute of Immunobiology, Kantonal Hospital, St. Gallen, Schweiz
  • Sanne Ea Jørgensen, Danmark
  • Hashaam Akhtar, Danmark
  • Piotr Siupka, Danmark
  • Thomas Pietschmann, Institute of Experimental Virology, TWINCORE- Centre for Experimental and Clinical, Infection Research, Hannover, Tyskland
  • Volker Thiel, Institute of Immunobiology, Kantonal Hospital, St. Gallen, Schweiz
  • Rune Hartmann
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNk4 ORF. The expression of IFNk4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNk4, which signals through the IFNkR1 and IL-10R2 receptor chains. Recombinant IFNk4 is antiviral against both HCV and coronaviruses at levels comparable to IFNk3. However, the secretion of IFNk4 is impaired compared to that of IFNk3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNk4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNk4 is strongly antiviral but a disadvantage during HCV infection.
OriginalsprogEngelsk
TidsskriftE M B O Journal
Vol/bind32
Sider (fra-til)3055-3065
Antal sider11
ISSN0261-4189
DOI
StatusUdgivet - 29 okt. 2013

    Forskningsområder

  • Interferon, Hepatitis, Immunologi

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