Background::Interferon kappa (IFN-κ) is a type I interferon (IFN-I) that inhibits virus replication by evoking interferon-stimulated genes (ISGs). However, as an evolutionarily ancient interferon, IFN-κ may function differently from the later emerged interferon-α and β.Methods::Conventional molecular biology methods were used to determine the localization of IFN-κ 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-κ or IFN-α2.Results::Human IFN-κ exists in two forms upon ectopic expression, one located on the cell membrane and the other secreted outside the cells. The membrane-anchored IFN-κ showed the ability to induce ISGs and curtail RNA virus replication, whereas the secreted IFN-κ 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-κ; the former influenced the expression and secretion of IFN-κ, and the latter had an impact on the induction of ISGs. In addition, prokaryotic purified soluble mature human IFN-κ was also capable of inducing ISGs and inhibiting RNA virus replication. Importantly, human IFN-κ induced a faster ISG response but with a lower intensity and a shorter half-life than the response of IFN-α2. In contrast, IFN-α2 started to function later but was stronger and more durable than IFN-κ.Conclusions::Human IFN-κ-induced ISG response and inhibited respiratory RNA virus replication dependent on cell-to-cell interactions. In addition, compared with IFN-α2, IFN-κ exerted effects more rapidly in the early phase, with less intensity and a shorter half-life. Therefore, IFN-κ may constitute the first line of IFN-I against respiratory virus infections.

Interferon type I;IFN-κ;Influenza;Mechanism;SARS-CoV-2

Fu Weihui;Sun Peng;Fan Jun;Ding Longfei;Yuan Songhua;Zhai Guanxing;Zhang Miaomiao;Qiu Chenli;Zhang Shuye;Zhang Xiaoyan;Xu Jianqing

Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China

感染性疾病和免疫（英文）

[1]Fu Weihui;Sun Peng;Fan Jun;Ding Longfei;Yuan Songhua;Zhai Guanxing;Zhang Miaomiao;Qiu Chenli;Zhang Shuye;Zhang Xiaoyan;Xu Jianqing-.Human IFN-κ Inhibited Respiratory RNA Virus Replication Dependent on Cell-to-Cell Interaction in the Early Phase)[J].感染性疾病和免疫（英文）,2022(02):65-73

27aa,37aa

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