Mechanisms Of Transcription Factor CREB Mediated Regulation Of Antiviral Immune Responses

Virus infects hosts will causes an immune response.The pathogen-associated molecular pattern is recognized by the host’s multiple pattern recognition receptors（PRRs）,which activates a series of cascades to induce Type I interferon（Type I IFNs）,inflammatory factors and downstream antiviral protein expression.These proteins activate the expression of a large number of downstream genes through various secretory pathways,thereby inhibiting virus replication and activating adaptive immunity to clear the virus.According to the composition of genetic material,viruses can be divided into DNA viruses and RNA viruses.In previous studies,it was found that knocking out of CREB（c AMP responsive element-binding protein,CREB）suppresses the expression of IL10 and promotes the replication of RNA viruses such as VSV&Se V.But whether it has an effect on DNA virus infection is unclear.This study mainly revealed whether CREB can play a role in DNA virus-mediated innate immune processes.We conducted a Western blot experiment and found that HSV-1 infection promotes phosphorylation of transcription factor CREB.In order to further study the mechanism of CREB in the anti-viral natural immunity process,we performed RNA-seq and Ch IP-seq sequencing and found that the expression of Il6was down-regulated after CREB knockout,and the binding ability of Il6 to CREB was weakened after HSV-1 stimulation.In vitro,the replication of viruses in CREB knock-out cells after HSV-1 stimulation is significantly increased,while the levels of type I interferon and inflammatory factors have different changes in different types of cells.In vivo,we constructed Creb^fl/flCre-ER mice and followed by injection of HSV-1 in the tail vein.It was found that Creb^+/+Cre-ER mice and Creb^fl/flCre-ER mice had no effect on the death caused by HSV-1 infection,and the levels of type I interferon and proinflammatory factors in the peripheral blood of the mice and the virus replication in the tissues did not change significantly.These results show that although CREB phosphorylation is induced by HSV-1,it does not affect the invasion of HSV-1.The difference between the results in vivo and in vitro may suggest that there may be other mechanisms inside the body that can resist the infection of HSV-1 to the body,and the detailed regulatory mechanisms still need more in-depth research.