Interferon Regulatory Factor 7 Replication Of Human Herpesvirus 8

Interferon regulatory factor 7(IRF7) has been identified as one of the major regulators in viral induced type I IFN production that is central to innate immunity. Thus, IRF7 plays important roles in a variety of biologic systems.In this study, we tried to figure out the influence of the IRF7 on the replication of Human herpesvirus 8(HHV-8). We found that IRF7 repressed the lytic replication of HHV-8, not only in the infection but also in the reactivation of the virus. IRF7 could be silenced by the method of RNAi, which removed the repression of IRF7 on the replication of HHV-8.The activity of IRF7 can be regulated by post-translational modifications, including acetylation, ubiquitination and sumoylation. Since these modifications usually happen on lysine residues of target proteins, we assumed that the functions of IRF7 could be highly affected by the mutation of lysine residues. In this study, lysine residues of IRF7 were changed into the arginine residues by site-directed mutagenesis. Wild type or mutant IRF7s were transfected into 293T cells and Vero cells in which a recombinant virus rKSHV.219 infected for the detections of activity of IRF7. We found that the lysine residues mutant affected the functions of IRF7, including the activation on type I IFN promoter, the suppression on RTA transactivation of the ORF57 promoter and the repression on the replication of HHV-8. Different mutants showed different effects upon the functions of the IRF7. Compared with the wild type IRF7, some mutants remained the functions of IRF7; some mutants weakened the functions of IRF7 while some mutants abolished the functions of IRF7.These results proved that IRF7 repressed the replication of HHV-8, and the lysine residues were involved in the regulation of IRF7 functions, which are of value of the further study of lysine residue related modifications of IRF7.