Our recent study reported that ATP1B3 inhibits hepatitis B virus(HBV)replication via inducing NF-κB activation.However,ATP1B3 mutants which were defective in NF-κB activation still maintained the moderate degree of ...Our recent study reported that ATP1B3 inhibits hepatitis B virus(HBV)replication via inducing NF-κB activation.However,ATP1B3 mutants which were defective in NF-κB activation still maintained the moderate degree of suppression on HBV replication,suggesting that another uncharacterized mechanism is also responsible for ATP1B3-mediated HBV suppression.Here,we demonstrated that ATP1B3 reduced the expression of HBV envelope proteins LHBs,MHBs and SHBs,but had no effect on intracellular HBV DNA,RNA levels as well as HBV promoter activities.Further investigation showed that proteasome inhibitor MG132 rescued ATP1B3-mediated envelope proteins degradation,demonstrating that proteasome-dependent pathway is involved in ATP1B3-induced degradation of envelope proteins.Co-IP showed that ATP1B3 interacts with LHBs and MHBs and induces LHBs and MHBs polyubiquitination.Immunofluorescence colocalization analysis confirmed LHBs and MHBs colocalized with ATP1B3 together.Our work provides important information for targeting ATP1B3 as a potential therapeutic molecule for HBV infection.展开更多
基金This work was supported by funding from the National Natural Science Foundation of China(81672004 and 31270202)the Chinese Ministry of Science and Technology(2018ZX10302104-001-010)+3 种基金Science and Technology Department of Jilin Province(20160101044JC and 20190101003JH)Health Commission of Jilin Province(2016J065)the Key Laboratory of Molecular Virology,Jilin Province(20102209)Norman Bethune Program of Jilin University(2015331)to Baisong Zheng.
文摘Our recent study reported that ATP1B3 inhibits hepatitis B virus(HBV)replication via inducing NF-κB activation.However,ATP1B3 mutants which were defective in NF-κB activation still maintained the moderate degree of suppression on HBV replication,suggesting that another uncharacterized mechanism is also responsible for ATP1B3-mediated HBV suppression.Here,we demonstrated that ATP1B3 reduced the expression of HBV envelope proteins LHBs,MHBs and SHBs,but had no effect on intracellular HBV DNA,RNA levels as well as HBV promoter activities.Further investigation showed that proteasome inhibitor MG132 rescued ATP1B3-mediated envelope proteins degradation,demonstrating that proteasome-dependent pathway is involved in ATP1B3-induced degradation of envelope proteins.Co-IP showed that ATP1B3 interacts with LHBs and MHBs and induces LHBs and MHBs polyubiquitination.Immunofluorescence colocalization analysis confirmed LHBs and MHBs colocalized with ATP1B3 together.Our work provides important information for targeting ATP1B3 as a potential therapeutic molecule for HBV infection.
