Ev71 Promotes The Expression Of Inflammatory Cytokines Via Epigenetic Modification

Enterovirus 71 is one of the human enteroviruses,which can lead to the Hand foot and mouth disease.The major targets of EV71 infection are children under 5 years old and infants.EV71 usually cause self limiting disease,but also can cause some severe complications such as encephalitis,poliomyelitis and other central nervous system diseases and pulmonary edema.DNA methylation is a kind of epigenentic modification,and DNA methytransferases(DNMTs)play important roles in regulating the expression of genes.This article mainly studies what role does DNMT play in the process that EV71 induces the inflammatory cytokines,and figures out the interaction between EV71 and DNMT.First,we find that 5-aza-dc(a kind of DNA methylation inhibitor)can up regulate the expressions of inflammatory cytokines in RD cell line,and the over expression of DNMT3 B can reduce the stimulation of inflammatory cytokines after EV71 infection.Then,we infect 1-day-old suckling mice with MA-EV71 and treat them with 5-aza-dc through IP method.We find that compared with the mice who were only infected with MA-EV71,those who were treated with both MA-EV71 and5-aza-dc have higher expression levels of IL-6 and TNF-α in serum.By studying the machenism of DNMT3 B in EV71 infection,we find that 3C and 3D can interact with DNMT3 B,unbind it from the promotor regions of IL-6 and TNF-α,and mediate the K63-linked polyubiquitination of DNMT3B.