ATP1B3 Restricts Hepatitis B Virus Replication Via Reducing the Expression of the Envelope Proteins

Abstract

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 co-localization 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.

Genome-wide detection of positive and balancing signatures of selection shared by four domesticated rainbow trout populations (Oncorhynchus mykiss)

“…In the heterozygous chr16_a region, the atp1b3 ( sodium/potassium-transporting ATPase subunit beta-1-interacting protein 3 ) gene was identified to be under positive selection in farmed Atlantic salmon [ 119 ]. This gene induces NF-kappa B activation to inhibit viral replication, such as for hepatitis B, HIV, and EV71 [ 163 , 164 ]. In addition, atp1b3a and atp1b3b paralogs have been hypothesized to be involved in the physiological response to low salinity in the Senegalese sole [ 165 ].…”

Genome-wide detection of positive and balancing selection signatures shared by four domesticated rainbow trout populations (Oncorhynchus mykiss)

“…In addition, this gene is involved in some immune responses. It was shown in cell culture study, that atp1b3 inhibits hepatitis B virus replication via inducing NF-kappa B activation (human: Zhang et al, 2021) and is involved in numerous viral propagation such as HIV and EV71 (Zheng et al, 2020 ) in cell culture experiments.…”