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Title: Activated macrophages promote hepatitis C virus entry in a tumor necrosis factor-dependent manner
Authors: Fletcher, N.F
Sutaria, R
Jo, J
Barnes, A
Blahova, M
Meredith, L.W
Cosset, F.-L
Curbishley, S.M
Adams, D.H
Bertoletti, A 
Mckeating, J.A
Keywords: CD81 antigen
gamma interferon
interleukin 10
interleukin 17
interleukin 18
interleukin 1beta
interleukin 4
interleukin 6
interleukin 8
messenger RNA
tight junction protein
tumor necrosis factor alpha
cell differentiation
cell membrane permeability
cell strain HepG2
controlled study
diffusion coefficient
hepatitis C
Hepatitis C virus
hepatoma cell
human cell
Human immunodeficiency virus
innate immunity
Kupffer cell
Lassa virus
liver cell
macrophage activation
Measles virus
priority journal
vesicular stomatitis
Vesicular stomatitis virus
virus entry
Antigens, CD81
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Polarity
Hep G2 Cells
Hepatitis C
Immunity, Innate
Liver Neoplasms
Macrophage Activation
Tight Junctions
Tumor Necrosis Factor-alpha
Virus Internalization
Issue Date: 2014
Publisher: John Wiley and Sons Ltd
Citation: Fletcher, N.F, Sutaria, R, Jo, J, Barnes, A, Blahova, M, Meredith, L.W, Cosset, F.-L, Curbishley, S.M, Adams, D.H, Bertoletti, A, Mckeating, J.A (2014). Activated macrophages promote hepatitis C virus entry in a tumor necrosis factor-dependent manner. Hepatology 59 (4) : 1320-1330. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Macrophages are critical components of the innate immune response in the liver. Chronic hepatitis C is associated with immune infiltration and the infected liver shows a significant increase in total macrophage numbers; however, their role in the viral life cycle is poorly understood. Activation of blood-derived and intrahepatic macrophages with a panel of Toll-like receptor agonists induce soluble mediators that promote hepatitis C virus (HCV) entry into polarized hepatoma cells. We identified tumor necrosis factor ? (TNF-?) as the major cytokine involved in this process. Importantly, this effect was not limited to HCV; TNF-? increased the permissivity of hepatoma cells to infection by Lassa, measles and vesicular stomatitis pseudoviruses. TNF-? induced a relocalization of tight junction protein occludin and increased the lateral diffusion speed of HCV receptor tetraspanin CD81 in polarized HepG2 cells, providing a mechanism for their increased permissivity to support HCV entry. High concentrations of HCV particles could stimulate macrophages to express TNF-?, providing a direct mechanism for the virus to promote infection. Conclusion: This study shows a new role for TNF-? to increase virus entry and highlights the potential for HCV to exploit existing innate immune responses in the liver to promote de novo infection events. © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.
Source Title: Hepatology
ISSN: 0270-9139
DOI: 10.1002/hep.26911
Rights: Attribution 4.0 International
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