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 differentl...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.展开更多
基金This work was supported by the National Science Foundation of China(No.82071788)Three-year Action Plan for Shenkang Clinical Research from Shanghai Municipal Health Commission(SHDC2020CR3011A)the Special Medical Innovation Research Project of“Scientific and Technological Innovation Action Plan”of Shanghai Municipal Commission of Science and Technology in 2020(20Y11900500).
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.
