The HBx gene of hepatitis B virus can influence hepatic microenvironment via exosomes by transferring its mRNA and protein

Kapoor, Neetu Rohit; Chadha, Radhika; Kumar, Saravanan; Choedon, Tenzin; Reddy, Vanga Siva; Kumar, Vijay

doi:10.1016/j.virusres.2017.08.009

Cited by 55 publications

(56 citation statements)

References 52 publications

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Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

“…Hepatitis B virus (HBV) infects human hepatocytes leading to liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma [ 55 , 56 ]. HBV’s HBx protein facilitates oncogenic activities via various mechanisms such as host gene stimulation, cell cycle interference, and mitogenic signaling [ 55 ]. Both HBx protein and associated mRNA encapsulated within exosomes released from HBV infected cells into the extracellular environment, permitting horizontal transfer of its gene products and viral protein expression [ 55 ].…”

Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

“…HBV’s HBx protein facilitates oncogenic activities via various mechanisms such as host gene stimulation, cell cycle interference, and mitogenic signaling [ 55 ]. Both HBx protein and associated mRNA encapsulated within exosomes released from HBV infected cells into the extracellular environment, permitting horizontal transfer of its gene products and viral protein expression [ 55 ]. HBx containing exosomes have significantly different cargo, both quantitatively and qualitatively [ 55 ].…”

Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

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Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

Caobi

Nair

Raymond

2020

Viruses

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Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review's scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.

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Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

Section: Role Of Evs In the Pathogenesis Of Viral Infectionsmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

Caobi

Nair

Raymond

2020

Viruses

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“…Although gastric cancer biomarkers and theranostics have made great advance [23,24,25,26]; some miRNAs have also been found to be associated with gastric cancer stages [27], how the exosomal proteins involved in the progression of cancer still lacks report. Li, et al reported that exosomal proteins were used for cancer diagnosis, were potential biomarkers [28], and could also be used for cardiac angiogenesis [29], tumor therapy [30] and (hepatitis B virus) HBV therapy [31]. Tumor cell-derived exosomes could be used for tumor therapy [32].…”

Section: Urinary Exosomes Proteomics Analysismentioning

confidence: 99%

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Yang¹,

Zhi²,

Liu³

et al. 2017

Nano BioMed ENG

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Urinary exosomes containing specific biomarkers have recently been considered as novel potential non-invasive candidates for renal disease diagnosis. However, the development of urinary exosomes in basic research and their subsequent diagnostic application are impeded by the lack of an efficient isolation method. One of the main challenges during urinary exosomes isolation is how to remove a large number of Tamm Horsfall proteins (around 92 kDa) and other biological components from exosome enrichment mixture. Herein, we report a facile and low-cost isolation method for highlypurified human urinary exosomes based on dialysis. The key protocol for exosome isolation includes only two steps: (1) Healthy person urines were collected. 10 mL urine in 300 kDa dialysis tubes was firstly dialyzed in phosphate-buffered saline solution three times for sequential nine hours; (2) The dialysis suspension was concentrated to 200 μL by using 100 kDa ultracentrifuge tubes to achieve urinary exosome isolation. For verification, the concentrated solution was examined by western blot, transmission electronic microscopy, atomic force microscopy and qNano, which demonstrated the highly-purified urinary exosomes were present. Furthermore, a total of 359 proteins were identified by the proteomic analysis of purified urinary exosomes from healthy persons. Those results demonstrated that highly-purified urinary exosomes could be achieved by our isolation method; 359 proteins were identified from healthy persons. Further works will focus on screening and identifying disease-related biomarkers from human urine exosomes for clinical diagnosis.

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“…In most cases, viral infection contributes to the development, invasion and metastasis of HCC (2), which is a global public health problem. In particular, chronic hepatitis B virus (HBV) is one of the leading causes of HCC with an estimated 400 million individuals currently affected by chronic infection worldwide (3,4). More than 50% of HCC cases arise from chronic HBV infections (5,6).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential key genes and pathways in hepatitis�B virus‑associated hepatocellular carcinoma by bioinformatics analyses

2020

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Chronic hepatitis B virus (HBV) is one of the leading causes of hepatocellular carcinoma (HCC). The precise molecular mechanisms by which HBV contributes to HCC development are not fully understood. The key genes and pathways involved in the transformation of nontumor hepatic tissues into HCC tissues in patients with HBV infection are essential to guide the treatment of HBV-associated HCC. Five datasets were collected from the Gene Expression Omnibus database to form a large cohort. Differentially expressed genes (DEGs) were identified between HCC tissues and nontumor hepatic tissues from HBV-infected patients using the 'limma' package. The top 50 upregulated and top 50 downregulated DEGs in HCC vs. nontumor tissues were demonstrated in subsets by heat maps. Based on the DEGs, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analyses were performed. Several key pathways of the up-and downregulated DEGs were identified and presented by protein-protein interaction (PPI) networks. A total of 1,934 DEGs were identified. The upregulated DEGs were primarily associated with the 'cell cycle'. Among the DEGs enriched in the 'cell cycle' pathway, 6 genes had a log 2-fold change >2: SFN, BUB1B, TTK, CCNB1, CDK1 and CDC20. The downregulated DEGs were primarily associated with the metabolic pathways, such as 'carbon metabolism', 'glycine, serine and threonine metabolism', 'tryptophan metabolism', 'retinol metabolism' and 'alanine, aspartate and glutamate metabolism'. The DEGs in the 'cell cycle' and 'metabolic pathways' were presented by the PPI networks respectively. Overall, the present study provides new insights into the specific etiology of HCC and molecular mechanisms for the transformation of nontumor hepatic tissues into HCC tissues in patients with a history of HBV infection and several potential therapeutic targets for targeted therapy in these patients.

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The HBx gene of hepatitis B virus can influence hepatic microenvironment via exosomes by transferring its mRNA and protein

Cited by 55 publications

References 52 publications

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

Extracellular Vesicles in the Pathogenesis of Viral Infections in Humans

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Identification of potential key genes and pathways in hepatitis�B virus‑associated hepatocellular carcinoma by bioinformatics analyses

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