Primary Research On The Mechanism Of Sox3 Inhibiting Virus-induced Type Ⅰ Interferon Production

Natural immunity used the Pattern recognition receptors(PRRs)expressed by the cells themselves to recognize pathogen-associated molecular patterns(PAMPs),initiate the signal cascade,Induces the production of cytokines such as type Ⅰ interferons and pro-inflammatory factors.Although the signal transduction of virus-induced type Ⅰ interferons has been studied in depth,there are still many problems waiting to be discovered and solved.For example,PTEN(Phosphatase and tensin homolog deleted on chromosome ten)as a tumor suppressor,in addition to playing a central role in tumor suppression,is also involved in the cellular antiviral natural immunity,PTEN through its phosphatase activity exerts dephosphorylation on IRF3 Ser97,thereby promoting IRF3 entry into the nucleus and activating type Ⅰ interferons expression.Whether PTEN is regulated by other proteins,and what regulatory mechanisms exist in the upstream of PTEN are still unclear.The transcription factor Sox3 belongs to the Sox(SRY-related HMG-box)family and is widely expressed in the central nervous system such as the ventral hypothalamus and spinal cord,and in some non-neural tissues.It is very important for the normal development of the nervous system and gender differentiation.Although Sox3 plays an indispensable role in embryonic development,the function of Sox3 in antiviral immunity has not been reported.In this study,we found a new function of the transcription factor Sox3 in antiviral innate immunity.Overexpression of Sox3 can inhibit the virus-induced IFN-β promoter’s activation and significantly inhibit the expression of type Ⅰ interferons in different stages of viral infection.Down-regulation of endogenous Sox3 expression promotes virus-induced IFN-β expression.through the Ch IP-seq assay We found that Sox3 binds to the promoter region of AKT1.Furthermore,we found that Sox3 can promote the expression of AKT1 gene,thereby Increased the phosphorylation of PTEN tail in the case of viral infection,leaving PTEN in a "low activity state",which leads to a decrease in the nuclear import of IRF3,thereby inhibiting the expression of type Ⅰ interferons.In conclusion,in addition to playing an important role in embryonic development,Sox3 is also involved in the antiviral natural immune response,our study further elucidating the signal transduction regulation mechanism of PTEN involved in type Ⅰ interferons expression.Of course,this may be just one of the manners for Sox3 to participate in antiviral innate immunity,and other molecular mechanisms by which Sox3 is involved in the antiviral natural immune response remain to be further studied.