Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses.
Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses.
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DOI：
10.1038/emboj.2013.232
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发表时间：
2013-11-27
期刊：
影响因子：
11.4
通讯作者：
Hartmann, Rune
中科院分区：
文献类型：
--
作者：
Hamming, Ole J.;Terczynska-Dyla, Ewa;Vieyres, Gabrielle;Dijkman, Ronald;Jorgensen, Sanne E.;Akhtar, Hashaam;Siupka, Piotr;Pietschmann, Thomas;Thiel, Volker;Hartmann, Rune
IFNL4基因是最近发现的III型干扰素，它在很大一部分人群中具有移码突变，可消除IFNλ4 ORF。ifn - λ4的表达与丙型肝炎病毒（HCV）自发清除率差以及对I型干扰素治疗的不良反应相关。在这里，我们发现IFNL4基因编码一种活性的III型干扰素，名为IFNλ4，它通过IFNλR1和IL-10R2受体链发出信号。重组ifn - λ4对HCV和冠状病毒的抗病毒水平与ifn - λ3相当。然而，与ifn - λ3相比，ifn - λ4的分泌受到损害，并且这种损害不是由于弱信号肽，这是之前认为的。我们发现ifn - λ4被n链糖基化，这种糖基化是分泌所必需的。然而，这种糖基化并不是活性所必需的。综上所述，这些发现导致了ifn - λ4在HCV感染期间具有强抗病毒作用但却处于劣势的悖论。
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 IFNλ4 ORF. The expression of IFNλ4 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 IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 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 IFNλ4 is strongly antiviral but a disadvantage during HCV infection.
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