Hepatitis C virus infection of cholangiocarcinoma cell lines

Fletcher, Nicola F.; Humphreys, E; Jennings, Elliott; Osburn, William O.; Lissauer, Samantha; Wilson, Garrick K.; IJzendoorn, Sven C. D. van; Baumert, Thomas F.; Balfe, Peter; Afford, Simon C.; McKeating, Jane A.

doi:10.1099/vir.0.000090

Cited by 8 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using HCVpp expressing a GFP reporter, we could demonstrate that HCVpp entry was restricted to hepatocyte-like cells, whereas Vesicular Stomatitis Virus encoded G expressing pseudoparticle (VSV-Gpp) infected cells with both hepatocyte and cholangiocyte morphology (data not shown). These observations were consistent with our previous report that primary cholangiocytes were not permissive for HCV infection [ 16 ]. Importantly, TNF-α, TNF-β, TWEAK and LIGHT increased the permissiveness of differentiated HepaRG cells to support HCVpp infection ( Fig.…”

Section: Resultssupporting

confidence: 94%

TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway

Fletcher

Clark

Balfe

et al. 2017

Journal of General Virology

View full text Add to dashboard Cite

Preventing virally induced liver disease begins with an understanding of the host factors that define susceptibility to infection. Hepatitis C virus (HCV) is a global health issue, with an estimated 170 million infected individuals at risk of developing liver disease including fibrosis and hepatocellular carcinoma. The liver is the major reservoir supporting HCV replication and this hepatocellular tropism is defined by HCV engagement of cellular entry receptors. Hepatocytes are polarized in vivo and this barrier function limits HCV entry. We previously reported that activated macrophages promote HCV entry into polarized hepatocytes via a TNF-α-dependent process; however, the underlying mechanism was not defined. In this study, we show that several TNF superfamily members, including TNF-α, TNF-β, TWEAK and LIGHT, promote HCV entry via NF-κB-mediated activation of myosin light chain kinase (MLCK) and disruption of tight junctions. These observations support a model where HCV hijacks an inflammatory immune response to stimulate infection and uncovers a role for NF-κB-MLCK signalling in maintaining hepatocellular tight junctions.

show abstract

Section: Resultssupporting

confidence: 94%

TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway

Fletcher

Clark

Balfe

et al. 2017

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Albeit limited number of virus infected ICC samples, our results implicate a potential skewness of COO depending on the virus infection status, and a separate cohort level study with larger number of samples is strongly warranted. In addition, these results also reflects the previous findings in differential infectivity of HBVs and HCVs for cholangiocytes (22, 23).…”

Section: Resultssupporting

confidence: 90%

Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer

Fujita

Yang

et al. 2019

Preprint

View full text Add to dashboard Cite

21Background: Primary liver tissue cancers display consistent increase in global disease burden 22 and mortality. Identification of cell-of-origins for primary liver cancers would be a necessity 23 to expand options for designing relevant therapeutics and preventive medicine for these cancer 24 types. Previous reports on cell-of-origin for primary liver cancers was mainly from animal 25 studies, and integrative research utilizing human specimen data was poorly established. 26Methods: We analyzed a whole-genome sequencing data set for a total of 363 tumor and 27 progenitor tissues along with 423 normal tissue epigenomic marks to predict the cell-of-origin 28 for primary liver cancer subtypes. 29Results: Despite the mixed histological features, the predicted cell-of-origin for mixed 30 hepatocellular carcinoma / intrahepatic cholangiocarcinoma were uniformly predicted as a 31 hepatocytic origin. Individual sample-level prediction revealed differential level of cell-of-32 origin heterogeneity depending on the primary liver cancer types, with more heterogeneity 33 observed in intrahepatic cholangiocarcinomas. Additional analyses on the whole genome 34 sequencing data of hepatic progenitor cells suggest these progenitor cells might not a direct 35 cell-of-origin for liver cancers. 36 Conclusions:These results provide novel insights on the heterogeneous nature and potential 37 contributors of cell-of-origin predictions for primary liver cancers. 38 39 Background 43Primary liver cancers (PLCs) is one of the major cancer types with increasing global disease 44 burden over the years, reaching incidence rates and mortality over 900,000 per year (1, 2). This 45 high morbidity and mortality of PLCs is due to the complex nature of the disease and lacking 46 effective diagnostics and treatment besides multi-kinase inhibitors, thus strongly emphasizing 47 the importance of relevant researches on early diagnosis and extensive drug development. In 48 line with this, several endeavored researches were performed on identifying suitable diagnostic 49 markers and targeted therapy-based treatments for PLCs, including the whole genome and 50 exome-level profiling (3). So far, recent comprehensive efforts on investigating the genomics 51 of PLCs revealed novel insights about the major mutation signatures, sub-classifications, and 52 recurrent somatic mutations in coding regions (TERT, TP53, CTNNB1, KRAS, IDH1/2, etc.) 53 and noncoding regions (NEAT1 and MALAT1), which some of them are driver mutations and 54 may associate with the clinical outcomes (4, 5). More investigations are underway to fully 55 unveil the mechanisms and processes behind the progression of PLCs. 56 One of the complex, unanswered questions associated with the progression of PLCs is the 57 possible cell-of-origins (COOs) corresponding to the various subtypes. PLC not only represents 58 classical hepatocellular carcinoma (HCC) subtype, comprising of ~90% of PLCs, but also 59 includes mixed hepatocellular and cholangiocarcinoma (Mixed) and intrahepatic 60 cholang...

show abstract

“…Pseudoviruses were generated by transfecting 293T cells with plasmids encoding a HIV-1 provirus expressing luciferase (pNL4-3-Luc-R-E-) and vesicular stomatitis virus (VSV-G), Zika, Ebola, Lassa or severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) envelope or a no-envelope control (Env−), as described previously [12,13]. ZIKV pseudoviruses were generated by amplifying the preM-M-Env region (positions 753-3549) from the PE243 Brazil Zika strain (accession no.…”

Section: Pseudovirus Generation and In Vitro Infectionmentioning

confidence: 99%

A novel antiviral formulation inhibits a range of enveloped viruses

Fletcher

Meredith

Tidswell

et al. 2020

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Some free fatty acids derived from milk and vegetable oils are known to have potent antiviral and antibacterial properties. However, therapeutic applications of short- to medium-chain fatty acids are limited by physical characteristics such as immiscibility in aqueous solutions. We evaluated a novel proprietary formulation based on an emulsion of short-chain caprylic acid, ViroSAL, for its ability to inhibit a range of viral infections in vitro and in vivo. In vitro, ViroSAL inhibited the enveloped viruses Epstein–Barr, measles, herpes simplex, Zika and orf parapoxvirus, together with Ebola, Lassa, vesicular stomatitis and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) pseudoviruses, in a concentration- and time-dependent manner. Evaluation of the components of ViroSAL revealed that caprylic acid was the main antiviral component; however, the ViroSAL formulation significantly inhibited viral entry compared with caprylic acid alone. In vivo, ViroSAL significantly inhibited Zika and Semliki Forest virus replication in mice following the inoculation of these viruses into mosquito bite sites. In agreement with studies investigating other free fatty acids, ViroSAL had no effect on norovirus, a non-enveloped virus, indicating that its mechanism of action may be surfactant disruption of the viral envelope. We have identified a novel antiviral formulation that is of great interest for the prevention and/or treatment of a broad range of enveloped viruses, particularly those of the skin and mucosal surfaces.

show abstract

Hepatitis C virus infection of cholangiocarcinoma cell lines

Cited by 8 publications

References 35 publications

TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway

TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway

Somatic mutation landscape reveals differential variability of cell-of-origin for primary liver cancer

A novel antiviral formulation inhibits a range of enveloped viruses

Contact Info

Product

Resources

About