There are many pattern recognition receptors(PRR)that exist in different cell types,pathogen-associated molecular pattems(PAMP)can be recognized by PRR,This process is an essential,early step in the innate immune response to pathogens.Herpes simplex virus type 1(HSV-1)as a large double strands DNA virus is ubiquitous during human.Upon recognition of HSV-1 infection,the innate immune responses are strongly activated by cellular PRR.A number of DNA sensors localized to a variety of sites within the cell can detect HSV-1 DNA.cGAS is an important DNA sensor during HSV-1 infection.Cytosolic DNA activates cGAS which synthesizes 2'3'-cGAMP,2'3'-cGAMP binds and activates STING,then recruits TBK1 to phosphorylate IRF3 and IKK complexs to activite NF-?B,then induce the production of type I IFNs and other cytokinesUL24 of HSV-1 is a tegument protein of 269 aa,and is required for efficient viral replication..Although UL24 has proved to play an important role in efficient infection,whether HSV-1 UL24 involves in the host innate immunity is poorly explored..In this study,UL24 was demonstrated to inhibit interferon stimulatory DNA mediated interferon-?(IFN-P)activation,and infection of UL24-null HSV-1 produced more IFN-? than that of wild-type HSV-1.UL24 also could inhibit cGAS-stimulator of interferon genes(STING)mediated IFN-p and canonical nuclear factor B(NF-?B)activation.The underlying mechanism is that UL24 bound to the NF-?B subunits p65 and abolished its nuclear translocation. |