The Identification And Classification Of Effective Interferon-stimulated Genes And The Antiviral Ability Of Interferon-downregulated Genes

Interferon(IFN)is an important cytokine,which plays an extremely critical defensive role in the process of eukaryotic cells responding to virus infection.IFN and its derivatives have also been used for a long time in the treatment of viral infectious disease.Although many researchers have extensively studied the IFN signal pathway and the antiviral function of downstream ISGs,the effective ISGs employed by IFN to resists the specific virus are still unclear.It is an important biological issue to clarify how IFN exercises its antiviral function by inducing effective ISGs.We analyzed the dynamic expression of ISGs which under IFN-α stimuli in HeLa cells,and identified the effective ISGs of three viruses including type I herpes simplex virus(HSV-1),vesicular stomatitis virus(VSV)and influenza A virus(IAV).We found that these proteins have the principles of dynamic expression pattern,specific antiviral ability,and the synergy effect.Therefore,we speculate that the antiviral IFN effective ISG may have a pattern effect similar to that of pattern recognition receptor.In order to verify the functional ISGs to HSV-1,VSV and IAV,we established an efficient CRISPR-Cas9 knockout system in HeLa cells,and used the gene-editing technology to identify and compare the effective ISGs.Moreover,we also found that the IFN down-regulated genes(IDGs),also have an impact on viral infection and proliferation.The function and mechanism of research on these proteins are likely to greatly promote the understanding and development of interferon-related research fields.