IFN-λ4与HCV感染最新研究进展

Relationship between IFN-λ4 and HCV infection

干扰素(interferon,IFN)为体内主要的抗病毒细胞因子,新发现的III型干扰素IFN-λ4与丙型肝炎病毒(HCV)的自发清除或治疗无效密切相关。IFN-λ4只能存在于携带IFNL4-ΔG等位基因(rs368234815)个体,它是预测HCV清除的最佳宿主因素。IFN-λ4也通过IFN-λ受体复合物传递信号,并通过激活JAK-STAT途径诱导干扰素刺激基因(IFN-stimulatedgene,ISG)的表达。IFN-λ4能诱导抗病毒活性,却同时影响了HCV的有效清除。因此,解决IFN-λ4这种看似矛盾的功能问题,可能会对HCV感染和干扰素生物学的免疫反应产生重要的新见解。

Interferons （IFNs） are generally considered antiviral cytokines, yet the recently discovered IFN-λ4 is linked with the failure to clear hepatitis C virus （HCV） infection either spontaneously or in response to treatment. IFN-λ4 can be generated only by individuals who carry the 1FNL4-△G allele （rs368234815）, which is the strongest known host factor for predicting clearance of HCV. IFN-λ4 signals through the IFN-λ, receptor complex and induces expression of IFN-stimulated genes via the Janus kinase-signal transducer and activator of transcription （JAK-STAT） signaling pathway. IFN-λ4 can induce antiviral activity yet impair ef- fective clearance of HCV. Resolving the paradoxical functions of IFN-λ4 may yield critical new insights into the immunologic response to HCV infection and IFN biology.