Study On The Relationship Between Varicella Zoster Virus(VZV) Infection And Autophagy

BackgroundVaricella-zoster virus(VZV)infection can cause chickenpox and herpes zoster,in the human body VZV can infect skin,nerves and lymphocytes,the mechanism ofVZV infection is still unclear.Autophagy is an intracellular degradation pathway,studies have shown that autophagy can defend against pathogen infection,while many pathogens,including several human herpes viruses,have evolved multiple mechanisms to evade,inhibit,and even utilize autophagy.Signal transducers and activators of transcription 3(STAT3)play an important role in regulating autophagy,and as transcription factors can regulate the replication and transmission of virus.ObjectiveTo study the relationship between VZV infection and autophagy,and the regulatory effect of STAT3 signaling pathway on autophagy and virus replication in VZV infection.Methods1.Flow cytometry was used to detect the expressions of autophagy protein LC3B,Beclin-1 and p62 in CD4 T lymphocytes of peripheral blood of 35 herpes zoster patients,30 healthy adults were used as the control group.Obtained the samples from the skin lesions of 12 herpes zoster patients,the expression of autophagy-related proteins in the skin tissue was detected by immunohistochemistry,and the formation of autophagosomes in the skin tissue was observed by transmission electron microscopy.2.In SHSY5Y cells infected by VZV,MDC fluorescence staining was used to observe autophagosomes,and western-blot was used to detect the expressions of autophagy proteins LC3B-?,Beclin-1 and p62.After treating infected cells with autophagy inducer trehalose or autophagy inhibitor 3-MA,the titer of VZV was detected,the expression of VZV glycoprotein E(gE)was detected by western-blot,and the DNA copy value of VZV was detected by q-PCR.3.The expression and phosphorylation of STAT3 and its downstream factor BNIP3 in VZV-infected-SHSY5Y cells were detected by western-blot.Changes in autophagy protein and VZV replication were detected while STAT3 pathway blocked by S3I-201.Trehalose,an autophagy inducer,was applied in VZV-infected SHSY5Y cells when STAT3 pathway was blocked by S3I-201,and then detect the changes on autophagy protein and VZV replicationResults1.The expression of autophagy protein LC3B and Beclin-1 in peripheral blood CD4+T cells and skin tissue of patients with herpes zoster were significantly increased(all P<0.05),and the expression of p62 was significantly decreased(P<0.05),the number of autophagosomes in skin lesions were significantly increased(P<0.05).2.The expression of autophagy protein LC3B and Beclin-1 in SHSY5Y cells infected with VZV was significantly increased(all P<0.05),and the expression of p62 was significantly decreased(P<0.05).After the induction/inhibition of autophagy,the viral titer was significantly increased/decreased,the VZV DNA copy value was significantly increased/decreased,and the expression of VZV gE was significantly increased/decreased(all P<0.05).3.In SHSY5Y cells infected with VZV,the expression and phosphorylation of STAT3,as well as the expression of its downstream factor BNIP3,were significantly increased(all P<0.05).When STAT3 was inhibited,the autophagy level of the cells was significantly decreased,and the replication of VZV was weakened,while autophagy inducer trehalose can reverse this decline(P<0.05).ConclusionAfter VZV infection,the level of autophagy increased in T lymphocytes,skin tissue and neurons,and the occurrence of autophagy had a positive effect on virus replication.Furthermore,the activation of the STAT3-BNIP3 pathway could regulate VZV replication by positively regulating the expression of autophagy in VZV infection.To explore the role of autophagy and its regulatory pathways in viral infectious diseases will provide insights into the mechanisms of viral replication and pathogeon-host interactions.