IFNL4: Notable variants and associated phenotypes().
IFNL4: Notable variants and associated phenotypes().
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DOI：
10.1016/j.gene.2019.144289
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发表时间：
2020-03-10
期刊：
影响因子：
3.5
通讯作者：
O'Brien TR
中科院分区：
文献类型：
--
作者：
Fang MZ;Jackson SS;O'Brien TR
干扰素λ蛋白激活JAK-STAT信号通路，导致具有抗病毒作用的基因上调。干扰素λ家族最初被认为是多余的干扰素α家族，通过相同的途径，除了更有限的IFNLR 1受体的表达信号。然而，最近的研究表明，干扰素单核苷酸独特地保护组织屏障免受广泛的重要病毒感染。干扰素λ 4基因（IFNL 4）于2013年被发现。IFNL 4蛋白由IFNL 4-ΔG/TT（rs368234815）变体决定。祖先IFNL 4-ΔG等位基因产生IFNL 4，而IFNL 4-TT导致蛋白质的过早终止。令人惊讶的是，尽管干扰素通常是抗病毒蛋白，但产生IFNL 4蛋白的基因型与丙型肝炎病毒（HCV）的清除受损密切相关。IFNL 4基因型也与HCV基因组内的变异以及肝纤维化、某些癌症和某些传染病的风险有关。针对祖先IFNL 4-ΔG等位基因的进化选择非常强烈，这是非洲人群中的主要形式，但在欧洲人和亚洲人中是次要等位基因。这种选择的原因和观察到的表型关联的生物学机制仍有待解释。
Interferon lambda proteins activate the JAK-STAT signalling pathway, resulting in upregulation of genes with antiviral effects. The interferon lambda family was initially thought to be redundant to the interferon alpha family, which signals through the same pathway, except for the more limited expression of the IFNLR1 receptor. However, recent studies show that interferon lambdas uniquely protect tissue barriers against a wide range of important viral infections. The interferon lambda 4 gene (IFNL4) was discovered in 2013. The IFNL4 protein is determined by the IFNL4-ΔG/TT (rs368234815) variant. The ancestral IFNL4-ΔG allele generates IFNL4, whereas IFNL4-TT causes pre-mature termination of the protein. Surprisingly, although interferons are generally antiviral proteins, the genotypes that generate the IFNL4 protein are strongly linked to impaired clearance of hepatitis C virus (HCV). IFNL4 genotype has also been linked to variation within the HCV genome, as well as risk of hepatic fibrosis, certain cancers and some infectious disease. There has been very strong evolutionary selection against the ancestral IFNL4-ΔG allele, which is the major form in African populations, but the minor allele in Europeans and Asians. The reason for this selection and the biological mechanisms underlying observed phenotypic associations remain to be explained.
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影响因子：
30.8
作者：
Ansari MA;Pedergnana V;L C Ip C;Magri A;Von Delft A;Bonsall D;Chaturvedi N;Bartha I;Smith D;Nicholson G;McVean G;Trebes A;Piazza P;Fellay J;Cooke G;Foster GR;STOP-HCV Consortium;Hudson E;McLauchlan J;Simmonds P;Bowden R;Klenerman P;Barnes E;Spencer CCA
通讯作者：
Spencer CCA
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
11.4
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
通讯作者：
Hartmann, Rune
DOI：
10.1097/qad.0000000000000052
发表时间：
2014-01-02
期刊：
AIDS (London, England)
影响因子：
--
作者：
Franco, Sandra;Aparicio, Ester;Martinez, Miguel Angel
通讯作者：
Martinez, Miguel Angel
影响因子：
6.7
作者：
Crotta S;Davidson S;Mahlakoiv T;Desmet CJ;Buckwalter MR;Albert ML;Staeheli P;Wack A
通讯作者：
Wack A