Using proteomics to identify the HBx interactome in hepatitis B virus: how can this inform the clinic?

Xie, Na; Chen, Xiang; Zhang, Tao; Liu, Bo; Huang, Canhua

doi:10.1586/14789450.2014.861745

Cited by 19 publications

(16 citation statements)

References 144 publications

(112 reference statements)

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“…Recent data has demonstrated that the transdifferentiation of quiescent HSCs into myofibroblasts activates glycolysis and results in lactate accumulation through the induction of HIF1-α for metabolic reprogramming of HSCs [40]. One of the main contributors in HBV infection is HBx protein that has been shown to interact with various host proteins [41, 42]. HIF-1α which is one of the interaction partners of HBx [43], activates the transcription of PKM [44].…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

et al. 2016

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BackgroundHepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers.MethodsTissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application.ResultsFibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1α (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis.ConclusionsTo our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1α can be a target pathway for novel therapeutic purposes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-017-0114-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

et al. 2016

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“…The regulation of transactivation activity by HBx relies on the interactions with several components of the basal transcriptional machinery, cellular sequence-specific transcription factors, or activation of signal transduction pathways. [9] However, the underlying molecular mechanism of HBx activating HBV replication are not fully understood. The "key" host proteins involved in HBx activating HBV transcription and replication are not fully understood.…”

Section: Clinical Relevancementioning

confidence: 99%

“…The trans‐acting transcriptional activity of HBx in enhancing HBV replication may depend on protein–protein interactions. The regulation of transactivation activity by HBx relies on the interactions with several components of the basal transcriptional machinery, cellular sequence‐specific transcription factors, or activation of signal transduction pathways . However, the underlying molecular mechanism of HBx activating HBV replication are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ‐Based Quantitative Comparative Proteomics

Yan

Zhang

et al. 2018

Proteomics Clinical Apps

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PurposeThe aim of this study was to screen for novel host proteins that play a role in HBx augmenting Hepatitis B virus (HBV) replication.Experimental designThree HepG2 cell lines stably harboring different functional domains of HBx (HBx, HBx‐Cm6, and HBx‐Cm16) were cultured. ITRAQ technology integrated with LC‐MS/MS analysis was applied to identify the proteome differences among these three cell lines.ResultsIn brief, a total of 70 different proteins were identified among HepG2‐HBx, HepG2‐HBx‐Cm6, and HepG2‐HBx‐Cm16 by double repetition. Several differentially expressed proteins, including p90 ribosomal S6 kinase 2 (RSK2), were further validated. RSK2 was expressed at higher levels in HepG2‐HBx and HepG2‐HBx‐Cm6 compared with HepG2‐HBx‐Cm16. Furthermore, levels of HBV replication intermediates were decreased after silencing RSK2 in HepG2.2.15. An HBx‐minus HBV mutant genome led to decreased levels of HBV replication intermediates and these decreases were restored to levels similar to wild‐type HBV by transient ectopic expression of HBx. After silencing RSK2 expression, the levels of HBV replication intermediates synthesized from the HBx‐minus HBV mutant genome were not restored to levels that were observed with wild‐type HBV by transient HBx expression.Conclusion and clinical RelevanceBased on iTRAQ quantitative comparative proteomics, RSK2 was identified as a novel host protein that plays a role in HBx augmenting HBV replication.

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“…HBx, encoded by the smallest ORF, is a non-structural viral protein consisting of 154 amino acids with a molecular weight of 17 kDa (1). Previous studies have indicated that HBx is a regulatory protein that benefits viral replication via interaction with numerous cellular proteins (2,3). Furthermore, HBx has an important role in HBV-mediated HCC progression by interacting with transcription factors, activating cellular signaling pathways or inducing aberrant epigenetic changes in order to alter cellular gene expression patterns and to contribute to hepatocarcinogenesis through various underlying mechanisms (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

The regulation of proteins associated with the cytoskeleton by hepatitis B virus X protein during hepatocarcinogenesis

et al. 2017

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Abstract. Hepatocellular carcinoma (HCC) is a major malignant disease worldwide, and chronic hepatitis B virus (HBV) infection is one of the primary causes for this type of cancer. Hepatitis B virus X protein (HBx) is a non-structural protein encoded by the viral genome that has significant effects on the pathogenesis of HCC. With the development of high-throughput assays and technologies, the abnormal HBx-induced expression of certain cellular proteins with assorted biological functions has been investigated. These target proteins identified by various methods include specific proteins associated with the cellular cytoskeleton, which contribute to HBx-induced hepatocarcinogenesis. In addition, the cytoskeletal proteins deregulated by HBx are involved in cell morphogenesis, adhesion, migration and proliferation. This review aims to summarize the current understanding of the expression profiles of HBx-associated cytoskeletal proteins, as well as their complex functions and underlying mechanisms in hepatocarcinogenesis. Considering that the potential therapeutics for various types of tumors may function through the stabilization of cytoskeletal proteins in order to restrict cellular movement and limit intracellular processes, clarifying the mechanisms underlying protein-associated cytoskeleton dysregulation by HBx may provide novel possibilities and potent therapeutic targets for HBV-associated HCC. Contents

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Using proteomics to identify the HBx interactome in hepatitis B virus: how can this inform the clinic?

Cited by 19 publications

References 144 publications

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages

Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ‐Based Quantitative Comparative Proteomics

The regulation of proteins associated with the cytoskeleton by hepatitis B virus X protein during hepatocarcinogenesis

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