Interaction between human cytomegalovirus UL136 protein and ATP1B1 protein

Zhang

Journal of Medical Virology

et al. 2019

Increasing evidence indicates ATP1B3, one of the regulatory subunits of Na+/K+‐ATPase, is involved in numerous viral propagations, such as HIV and EV71. However, the function and mechanism of ATP1B3 on hepatitis B virus (HBV) propagation is unknown. Here, we demonstrated that ATP1B3 overexpression reduced the quantity of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in supernatants of HBV expression plasmids cotransfected HepG2 cells. Correspondingly, small interfering RNA and short hairpin RNA mediated ATP1B3 silencing promoted HBsAg and HBeAg expression in the supernatants of HBV expression plasmids transfected HepG2 cells. Mechanically, we reported that ATP1B3 expression could activate nuclear factor‐κB (NF‐κB) pathway by inducing the expression, phosphorylation, and nuclear import of P65 for the first time. And NF‐κB inhibitor (Bay11) impaired the restraint of ATP1B3 on HBV replication. This counteraction effect of Bay11 proved that ATP1B3‐induced NF‐κB activation was crucial for HBV restriction. Accordingly, we observed that anti‐HBV factors interferon‐α (IFN‐α) and interleukin‐6 (IL‐6) production were increased in HepG2 cells after the NF‐κB activation. It suggested that ATP1B3 suppressed HBsAg and HBeAg by NF‐κB/IFN‐α and NF‐κB/IL‐6 axis. Further experiments proved that ATP1B3 overexpression induced anti‐HBV factor BST‐2 expression by NF‐κB/IFN‐α axis in HepG2 cells but not HEK293T cells, and ATP1B3 silencing downregulated BST‐2 messenger RNA level in HepG2 cells. As an HBV restriction factor, BST‐2 cooperated with ATP1B3 to antagonize HBsAg but not HBeAg in HepG2 cells. Our work identified ATP1B3 as a novel candidate of HBV restrictor with unrevealed mechanism and we highlighted it might serve as a potential therapeutic molecule for HBV infection.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ATP1B3 cooperates with BST‐2 to promote hepatitis B virus restriction

Zhang

Journal of Medical Virology

et al. 2019

“…Previous studies have shown that some subunits of Na þ /K þ -ATPase can interact with various viral proteins and affect the replication of viruses. It has been demonstrated that ATP1B1 subunit interacts with HCMV UL136 protein, M2 proteins of influenza A and B viruses and inhibit the virus replication (Cui et al, 2011;Mi et al, 2010). ATP1A1 has also been reported to inhibit entry of coronavirus into host cells by regulating the Src signaling pathway (Burkard et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

ATP1B3: a virus-induced host factor against EV71 replication by up-regulating the production of type-I interferons

Hou

Qiao

et al. 2016

Virology

Enterovirus 71 (EV71) infection can cause severe diseases, and is becoming increasingly common in children. In the current study, we carried out yeast two-hybrid assays to screen human proteins that could interact with 3A protein of EV71. Human β3 subunit of Na(+)/K(+)-ATPase (ATP1B3) protein was demonstrated to interact with the 3A protein of EV71. Although 3A protein had no effect on the expression of ATP1B3, EV71 infection resulted in elevated expression of ATP1B3 in RD cell line, both on messenger RNA (mRNA) and protein levels. Interestingly, knockdown of ATP1B3 could significantly increase the replication of EV71, whereas overexpression of ATP1B3 significantly suppressed the replication of EV71 in RD cells. Furthermore, we demonstrated that the expression of ATP1B3 could induce the production of type-I interferons. Our study demonstrated that ATP1B3 inhibit EV71 replication by enhancing the production of type-I interferons, which could act as a potential therapeutic target in EV71 infection.

“…Such course of the disease is attributed to airway remodeling, a process of structural changes of bronchi including loss of epithelial apical-to-basolateral polarity, epithelial sheathing, subepithelial brosis, epithelial-mesenchymal and broblast-to-myo broblast transition, hyperplasia of smooth muscle and goblet cells, neovascularization and cartilage degeneration 1 , leading to hyperresponsiveness and persistent air ow limitation. Current treatment options have limited in uence on remodeling and do not target it directly as mechanisms underlying the process are still investigated 23 . Since no accurate biomarker or clinical predictor of ongoing remodeling was agreed upon to date, there are no methods of selecting patients who could bene t the most from future experimental e.g.…”

mentioning

confidence: 99%

Integration of Airway Inflammation and Remodeling Mechanisms Specific to Eosinophilic Asthma Through Differential Co-Expression of Genes in Bronchial Brush Biopsy Samples

Koźlik

Buregwa-Czuma

Zawlik

et al. 2021

Preprint

Background Heterogeneity of asthma complicates search for targeted treatment against airway hyperresponsiveness and remodeling. We conducted a systems biology approach study to establish differential co-expression of genes (DCG) in eosinophilic and non-eosinophilic asthma patients and infer their role in the disease. Materials and Methods N = 40 Caucasian adult moderate to severe non-smoking asthma patients (half with eosinophilic asthma) undergone bronchial brush biopsy sampling for mRNA expression using hybridization to cDNA microarray. Mechanistic interpretation of DCG was inferred from existing literature. Results Differentially co-expressed genes bear significance in airway viral infection (ATP1B1, EPS15), arachidonic acid metabolism (CLC, FADS6), cell migration (EPS8L1, STOML3, RhoBTB2), surface receptors endocytosis (STRN4, EPS15, ATP1B1) or decreased expression (CCT7), oxidative stress (DIO3, RhoBTB2), decreased adhesion (ATP1B1, RAPH1, STOML3), epithelial-mesenchymal transition (ASB3, RADX, CCT7, MRPL14, PPP2R3B, RPS13, SLC19A1), myofibroblast differentiation (CCT7), smooth muscle proliferation (ASB3, ATP1B1), airway hyperreactivity (RECK, STOML3, ATP1B1, OR52I1), extracellular matrix remodeling (FBN3, RECK), angiogenesis (GPI, RhoBTB2) and neuronal pathogenesis of asthma (OR52I1, STRN4, TTC3P1, GPI, CABP5) and were linked to asthma in genome- (MRPL14, ASB3, RPS13) and epigenome-wide (CLC, EPS15, GPI, SSCRB4, STRN4) association studies. Signaling pathways involved (especially TGF-β/Smad2/3) are inferred from the co-expression pattern. Conclusion Activity of genes and pathways of known or tentative role in asthma pathogenesis was established in regard to a condition cognizable in clinical practice.