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Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

ABSTRACT: Based on our recently developed 5 chemicals-cultured primary human hepatocytes (5C-PHH) model that supports long-term HBV infection, we performed multiplexed quantitative analysis of temporal changes of host proteome and transcriptome on PHH cells infected by HBV for up to 4 weeks. We showed that metabolic-, complement-, cytoskeleton-, mitochondrial- and oxidation-related pathways were modulated at transcriptional or post-transcriptional levels during long-term HBV infection, which led to cytopathic effects and could be partially rescued by early rather than late nucleot(s)ide analogs (NAs) administration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183156 | GEO | 2021/09/02

REPOSITORIES: GEO

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Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes and Can be Partially Reversed by Antiviral Therapy

Project description:Global temporal quantitative proteomic and transcriptomic analysis using long-term hepatitis B virus (HBV)-infected primary human hepatocytes uncovered extensive remodeling of host proteome and transcriptome, and revealed cytopathic effects of long-term viral replication. Metabolic-, complement-, cytoskeleton-, mitochondrial- and oxidation-related pathways were modulated at transcriptional or post-transcriptional levels, which could be partially rescued by early rather than late nucleot(s)ide analogs (NAs) therapy. Overexpression screening identified a series of pro- or anti- HBV host factors. These data have deepened the understanding of the mechanisms of viral pathogenesis and HBV-host interactions in hepatocytes, with implications for therapeutic intervention.

2021-08-31 | PXD028190 | iProX

Rimonabant suppresses RNA transcription of hepatitis B virus by inhibiting HNF4α

Project description:The emergence of drug-resistant viruses against nucleot(s)ide analogs (NAs), which are the main treatment for chronic hepatitis B virus (HBV) infection, has become a problem. To discover novel anti-HBV compounds with a low risk of emergence of drug-resistant viruses, we performed screening of a G protein-coupled receptor-associated compound library and identified Rimonabant as a candidate. Transcriptome analysis of Rimonabant-treated primary hepatocytes by RNA sequencing revealed that the transcriptional activity of HNF4α, which is known to stimulate viral RNA synthesis, was depressed.

2020-01-26 | GSE139597 | GEO

ChIP-Seq data of H3K79succ modification of mononuclear bodies in PHH cells infected with HBV

Project description:Cell: HBV-infected PHH cells. Methods: PHH cells were infected with 2000 genome equivalents/cell of HBV particles in the presence of 4% PEG8000. Seven days after HBV infection, ChIP-Seq analysis of cccDNA in HBV-infected PHHs was carried out. HBV-infected PHH cells were digested with micrococcal nuclease and resulting mononucleosomes purified by sucrose gradient centrifugation. Nucleosomes were enriched with anti-H3K79succ antibodies by ChIP assay and the associated DNA contained both human and HBV DNA fragments was analyzed by deep sequencing. The HBV-specific reads in ChIP-Seq pilot experiments was quantified and normalized by the reads mapped to the human genome.

2021-11-14 | GSE188634 | GEO

Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

Project description:Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

| PRJNA798727 | ENA

Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

Project description:Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

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RNA-seq of HBV-infected Primary Human Hepatocytes treatment by Tazarotene

Project description:Monitor HBV mRNA reduction in response to Tazarotene and to identify global transcriptome-wide gene expression associated with Tazarotene treatment in HBV infected PHH using RNA-Seq

2018-09-09 | GSE114003 | GEO

RNA Expression Profile of HBV-infected Primary Human Hepatocytes treatment by Interferon subtypes.

Project description:Microarray-dependent transcriptional analysis of interferon stimulated genes treated with different kind of interferon subtypes in HBV-infected PHH.

2020-04-20 | GSE138566 | GEO

Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

Project description:Transcriptomic analysis was then applied to identify genes or pathways that could be rescued by RNAi.

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Comparative analysis of serum proteins between hepatitis B virus genotype B and C infection DIA-based quantitative proteomics

Project description:Hepatitis B virus (HBV) is an enveloped, coated, non-cytopathic and hepatotropic partially double-stranded DNA virus in the family Hepadnaviridae genus Orthohepadnavirus. Despite significant progress in the availability of safe vaccines and antiviral therapies against HBV, it still affects approximately 257 million people worldwide and is responsible for about 887,000 deaths per year around the world [4]. HBV infection, which are associated with acute and chronic liver failure responses to viruses attacked the liver, can result in inactive carrier state, chronic hepatitis, or fulminant hepatitis and put them at high risk to develop advanced liver fibrosis and cirrhosis, and even hepatocellular cancer. Many viral factors, which could affect the disparity of clinical outcomes or disease prognosis during chronic HBV infection, have been reported in previous studies; among them, the viral genotype, as well as HBV mutations ascribing the virus to a certain phenotype, was reported to be the most important factor influencing viral pathogenesis, including the change of host immune recognition, the enhanced virulence with increased HBV replication and the facilitation of cell attachment or penetration.

2022-02-17 | PXD025968 | Pride

Deciphering hepatitis B virus phospho-signature in primary human hepatocytes

Project description:Phosphorylation is a major post-translation modification (PTM) of proteins, and small molecules, which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either help or counteract viral replication. Surprisingly, among more than 500 kinases constituting the human kinome only few have been described as important for the Hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core protein (HBc) protein. In addition, scarce information is available on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape at early after infection. For this, primary human hepatocytes (PHH) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phospho-proteomic analysis was conducted two- and seven-days post-infection.

2024-05-02 | PXD051216 | Pride

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