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

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TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway. / Fletcher, Nicola; Clark, Andrew R; Balfe, Peter; McKeating, Jane.

In: Journal of General Virology, Vol. 98, No. 3, 01.03.2017, p. 405-412.

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@article{aaf5f855b2874ab5bdf4096d2c41fad3,
title = "TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway",
abstract = "Preventing viral 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 polarised in vivo and this barrier function limits HCV entry. We previously reported that activated macrophages promote HCV entry into polarised 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 signaling in maintaining hepatocellular tight junctions.",
author = "Nicola Fletcher and Clark, {Andrew R} and Peter Balfe and Jane McKeating",
year = "2017",
month = mar,
day = "1",
doi = "10.1099/jgv.0.000689",
language = "English",
volume = "98",
pages = "405--412",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Microbiology Society",
number = "3",

}

RIS

TY - JOUR

T1 - TNF superfamily members promote hepatitis C virus entry via an NF-κB and myosin light chain kinase dependent pathway

AU - Fletcher, Nicola

AU - Clark, Andrew R

AU - Balfe, Peter

AU - McKeating, Jane

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Preventing viral 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 polarised in vivo and this barrier function limits HCV entry. We previously reported that activated macrophages promote HCV entry into polarised 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 signaling in maintaining hepatocellular tight junctions.

AB - Preventing viral 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 polarised in vivo and this barrier function limits HCV entry. We previously reported that activated macrophages promote HCV entry into polarised 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 signaling in maintaining hepatocellular tight junctions.

U2 - 10.1099/jgv.0.000689

DO - 10.1099/jgv.0.000689

M3 - Article

C2 - 27983476

VL - 98

SP - 405

EP - 412

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 3

ER -