| 6 | Human IFN-k Inhibited Respiratory RNA Virus Replication Dependent on Cell-to-Cell Interaction in the Early Phase显示文摘Background:Interferon kappa(IFN-k)is a type I interferon(IFN-I)that inhibits virus replication by evoking interferon-stimulated genes(ISGs).However,as an evolutionarily ancient interferon,IFN-k may function differently from the later emerged interferon-a and b.Methods:Conventional molecular biology methods were used to determine the localization of IFN-k and its structure and function.In addition,we employed RT-PCR,western blot,and RNA-Seq technologies to characterize the ISGs expression profile and antiviral activities exerted by IFN-k or IFN-a2.Results:Human IFN-k exists in two forms upon ectopic expression,one located on the cell membrane and the other secreted outside the cells.The membrane-anchored IFN-k showed the ability to induce ISGs and curtail RNA virus replication,whereas the secreted IFN-k failed to do so.Structural analyses indicated that 1-27aa at the N-terminus was the signal peptide,and 28-37aa was predicted as the transmembrane region.However,our data demonstrated that both of them were not associated with membrane localization of IFN-k;the former influenced the expression and secretion of IFN-k,and the latter had an impact on the induction of ISGs.In addition,prokaryotic purified soluble mature human IFN-k was also capable of inducing ISGs and inhibiting RNA virus replication.Importantly,human IFN-k induced a faster ISG response but with a lower intensity and a shorter half-life than the response of IFN-a2.In contrast,IFN-a2 started to function later but was stronger and more durable than IFN-k.Conclusions:Human IFN-k-induced ISG response and inhibited respiratory RNA virus replication dependent on cell-to-cell interactions.In addition,compared with IFN-a2,IFN-k exerted effects more rapidly in the early phase,with less intensity and a shorter half-life.Therefore,IFN-k may constitute the first line of IFN-I against respiratory virus infections. | Weihui Fu Peng Sun Jun Fan Longfei Ding Songhua Yuan Guanxing Zhai Miaomiao Zhang Chenli Qiu Shuye Zhang Xiaoyan Zhang Jianqing Xu | 2022 | Infectious Diseases & Immunity2022，2，2： | 0 |
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