Research On The Decreased Aggregation Of MHtt Result From The Autophagy Induced By The VP₂ Structure Protein Of The Foot-and-mouth Disease Virus

The foot-and-mouth disease virus?FMDV?is a virus which can cause acute,thermotaxis and highly contagious disease of the cloven animals.And cell autophagy is a highly conservative way to control the degradation of intracellular proteins and organelles,it plays an important role in cell survival and development,to maintain steady state.Previous studies have reported that autophagy is also associated with a variety of human diseases.Previous studies have reported that FMDV infection induces cell autophagy.The lab study before reported FMDV infection induced a complete process of autophagy in FMDV natural host cell PK-15,and the inhibition of autophagy can significantly reduce the replication of FMDV,suggesting that FMDV induced autophagy is necessary for replication of the virus.And,during the FMDV infection,the EIF2?-ATF4 pathway was activated,and the AKT-mTOR pathway was suppressed.But it is not clear whether the FMDV induced autophagy rely on replication of the virus.In this thesis,to determine whether FMDV induced autophagy requires virus replication,We detected the occurrence of autophagy in UV-FMDV infected PK-15 cell by using WB.The experimental results showed that the UV-FMDV also induces cell autophagy.It illustrated that replication of the virus isn't necessary for FMDV induced autophagy.Then,we builded the expression plasmid of the FMDV structural protein VP₂,and determined that FMDV structural protein VP₂ also induces cell autophagy.And then,it detected the mechanism of VP₂ induced autophagy by WB which bear out that the FMDV structural protein VP₂ can induce autophagy through the EIF2?/ATF4/AKT/mTOR cascade.In addition,experimental results showed the VP₂ can induce autophagy in a variety of mammalian cell lines,and reduced the simulated mutate on of glutamine expansion protein polymer?Htt103Q?together.Overall,results of this study confirmed the FMDV capsid protein VP₂ can induce autophagy by EIF2?/ATF4/AKT/mTOR cascade,and which may be as a new potential therapeutic molecules for human diseases.