mitochondrial HBV X

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, thereby promoting HBV escape from the human innate immune system and establishing persistent infection. However, whether X proteins of Orthohepadnavirus viruses in other species display a similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts...

Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue...

Mitophagy, as an important link in maintaining mitochondrial homeostasis and environmental homeostasis in the liver, can remove damaged mitochondria and provide energy through autophagy and other processes. Additionally, it plays a dual role in the occurrence and development of liver cancer and can affect the therapeutic effect of liver cancer through a variety of signaling pathways. This article reviews the relationship between mitophagy and hepatitis B virus infection, liver cancer occurrence and development, liver cancer stem cells, mitochondrial division and fusion, therapeutic resistance and invasiveness of liver cancer, and other aspects...

STUDY QUESTION: What is the impact of male hepatitis B virus (HBV) infection on sperm quality, embryonic development, and assisted reproductive outcomes? SUMMARY ANSWER: Male HBV infection did not affect assisted reproductive outcomes, but HBV is capable of impairing human sperm and embryo formation in the early stages following fertilization. WHAT IS KNOWN ALREADY: HBV is found in germ cells and early embryos of patients with HBV. HBV may impair human sperm function via increasing reactive oxygen species...

Hepatitis B virus (HBV) infection is an important public health concern, as approximately 3.5% of the world's population is currently chronically infected. Chronic HBV infection is the primary cause of cirrhosis, hepatocellular carcinoma, and deaths related to liver disease globally. Studies have found that in HBV infection, viruses can directly or indirectly regulate mitochondrial energy metabolism, oxidative stress, respiratory chain metabolites, and autophagy, thereby altering macrophage activation status, differentiation types, and related cytokine secretion type and quantity regulations...

BACKGROUND & AIMS: Pegylated interferon alpha (pegIFNα) is commonly used for the treatment of people infected with HDV. However, its mode of action in HDV-infected cells remains elusive and only a minority of people respond to pegIFNα therapy. Herein, we aimed to assess the responsiveness of three different cloned HDV strains to pegIFNα . We used a previously cloned HDV genotype 1 strain (dubbed HDV-1a) that appeared insensitive to interferon-α in vitro , a new HDV strain (HDV-1p) we isolated from an individual achieving later sustained response to IFNα therapy, and one phylogenetically distant genotype 3 strain (HDV-3)...

BACKGROUND: Excessive alcohol intake with hepatitis B virus (HBV) infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease. Hepatitis B virus X protein (HBx) plays a crucial role in disease pathogenesis, while its specific role in alcoholic liver disease (ALD) progression has not yet been elucidated. Here, we studied the role of HBx on the development of ALD. METHODS: HBx-transgenic (HBx-Tg) mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding...

It is widely accepted that hepatitis B virus (HBV) integrants in the human genome are one of the key factors in liver carcinogenesis. Although it is difficult to observe pre/post-HBV infection genomic-level changes in the same clinical sample pairs, they can be observed using artificially infected HBV cell lines such as HepG2.2.15. A detailed HBV integration analysis comparing HepG2.2.15 with HepG2 cells, especially their mitochondrial (mt) DNA, was conducted using next-generation sequencing (NGS)-based integration analysis...

Chronic hepatitis B virus infection is the dominant cause of hepatocellular carcinoma, the main cause of cancer death. HBx protein, a multifunctional protein, is essential for pathogenesis development; however, the underlying mechanisms are not fully understood. The complexity of the system itself, and the intricate interplay of many factors make it difficult to advance in understanding the mechanisms underlying these processes. The most obvious solution is to use simpler systems by reducing the number of interacting factors...

Patients who are carriers of the hepatitis B virus (HBV) are at high risk of chronic liver disease (CLD) which proceeds from hepatitis, to fibrosis, cirrhosis and to hepatocellular carcinoma (HCC). The hepatitis B-encoded X antigen, HBx, promotes virus gene expression and replication, protects infected hepatocytes from immunological destruction, and promotes the development of CLD and HCC. For virus replication, HBx regulates covalently closed circular (ccc) HBV DNA transcription, while for CLD, HBx triggers cellular oxidative stress, in part, by triggering mitochondrial damage that stimulates innate immunity...

BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB). APPROACH AND RESULTS: The study included 146 treatment-naïve CHB mono-infected patients. Patients with CHB and advanced fibrosis (AF) or cirrhosis (F3-F4) were compared to patients with no/mild-moderate fibrosis (F0-F2)...

BACKGROUND & AIMS: The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-β induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyze the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up. METHODS: Children with CHB in the immune-tolerant phase were recruited and followed longitudinally...

Objectives: This study was designed to investigate whether HBx-induced podocyte injury is related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and the specific mechanism of the oxidative stress pathway in hepatitis B virus-associated glomerulonephritis (HBV-GN). Materials and Methods: The HBx gene was overexpressed in renal podocytes to mimic HBV-GN. Podocyte morphology was observed under a scanning electron microscope...

Objective: To analyze the characteristics of clinical and laboratory indexes in patients with liver disease with positive anti-liver cytosol antibody type 1 (anti-LC1), in order to provide references for clinical and differential diagnosis. Methods: The clinical data of 23 832 inpatients and outpatients with positive anti-LC1 autoantibodies detected in routine autoantibody test from January 2010 to January 2020 were retrospectively analyzed, and their clinical and laboratory indexes were compared. Western blotting was used to detect anti-LC1, anti-soluble liver antigen antibody (anti-SLA), anti-glycoprotein 210 antibodies and anti-nucleosome 100 antibodies...

Hepatocellular carcinoma (HCC) is developed from uncontrolled cell growth after the malignant transformation of hepatocytes. The hepatitis B virus (HBV) X protein (HBx) has shown to induce cell cycle progression and hepatocarcinogenesis. A sub-fraction of HBx is localized in the mitochondria. Sirtuin 4 (SIRT4), a mitochondrial protein, has been demonstrated to play a tumor-suppressive role in many cancers, including HCC. However, little is known about the association between mitochondrial HBx and SIRT4 during hepatocarcinogenesis...

Hepatitis B virus X protein C-terminal 127 amino acid truncation is often found expressed in hepatocellular carcinoma (HCC) tissue samples. The present in vitro study tried to determine the role of this truncation mutant in the hepatitis B-related liver diseases such as fibrosis, cirrhosis, HCC, and metastasis. HBx gene and its 127 amino acid truncation mutant were cloned in mammalian expression vectors and transfected in human hepatoma cell line. Changes in cell growth/proliferation, cell cycle phase distribution, expression of cell cycle regulatory genes, mitochondrial depolarization, and intracellular reactive oxygen species (ROS) level were analyzed...

Genotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage. We provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released and translocated to nuclei to sustain nDNA damage in a TET (tet methylcytosine dioxygenase)-dependent manner...

Hepatitis B X-interacting protein (HBXIP) is a conserved protein of 19 kDa that was originally identified as a binding partner of hepatitis B virus X protein. Emerging evidence indicates that HBXIP is highly expressed in a variety of cancers and is correlated with poor clinical outcomes in cancer patients. HBXIP plays a critical role in cancer progression, but the underlying mechanisms are still unclear. In this review, we primarily focus on publications investigating HBXIP in cancer research, including its expression and clinical significance in cancer patients, its role as a coactivator of transcription factors in cancer cells, its inhibitory effects on the mitochondrial cytochrome c-caspase apoptotic pathway, as well as its roles in promoting mitosis and drug resistance in cancer cells, its regulatory effects on cancer metabolism, and its relationships with other signaling pathways or microRNAs in cancer...

OBJECTIVE: Hepatitis B virus X protein (HBx) is a pivotal factor for HBV-induced hepatitis. Herein, we sought to investigate HBx-mediated NLR pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis under oxidative stress. METHODS: The effect of HBx on the NLRP3 inflammasome was analyzed by enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence in hepatic HL7702 cells...

In previous studies, we showed two consistent findings regarding the functional relationship between hepatitis B virus (HBV) gene expression and hepatic lipid accumulation. One is that HBV X (HBx) protein expression induces hepatic lipid accumulation via specific transcriptional activation. The other is that hepatic rich lipids increase HBV gene expression. A variety of transcription factors, including nuclear receptors have been defined as regulators of HBV promoters and enhancers. However, the association between these metabolic events and HBV gene expression remains to be clearly elucidated...