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Expression of human ficolin-2 in hepatocytes confers resistance to infection by diverse hepatotropic viruses

Irving, William L.; Jalal, Paywast J.; Urbanowicz, Richard A.; Horncastle, Emma; Pathak, Monika; Goddard, Chun; Saeed, Amanj; Mason, Christopher P.; Ball, Jonathan K.; McClure, C. Patrick; King, Barnabas J.; Tarr, Alexander W.

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Authors

Paywast J. Jalal

Richard A. Urbanowicz

Emma Horncastle

Chun Goddard

Amanj Saeed

Christopher P. Mason

JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology

Barnabas J. King



Abstract

The liver-expressed pattern recognition receptors (PRRs) mannose binding lectin (MBL), ficolin-2 and ficolin-3 contribute to the innate immune response by activating complement. Binding of soluble ficolin-2 to viral pathogens can directly neutralize virus entry. We observed that the human hepatoma cell line HuH7.5, which is routinely used for the study of hepatotropic viruses, is deficient in expression of MBL, ficolin-2 and ficolin-3. We generated a cell line that expressed and secreted ficolin-2. This cell line (HuH7.5 [FCN2]) was more resistant to infection with hepatitis C virus (HCV), ebolavirus (EBOV) and vesicular stomatitis virus (VSV), but surprisingly was more susceptible to infection with rabies virus (RABV). Cell-to-cell spread of HCV was also inhibited in ficolin-2 expressing cells. This illustrates that ficolin-2 expression in hepatocytes contributes to innate resistance to virus infection, but some viruses might utilise ficolin-2 to facilitate entry.

Citation

Irving, W. L., Jalal, P. J., Urbanowicz, R. A., Horncastle, E., Pathak, M., Goddard, C., …Tarr, A. W. (2019). Expression of human ficolin-2 in hepatocytes confers resistance to infection by diverse hepatotropic viruses. Journal of Medical Microbiology, 68(4), 642-648. https://doi.org/10.1099/jmm.0.000935

Journal Article Type Article
Acceptance Date Jan 15, 2019
Online Publication Date Feb 12, 2019
Publication Date Apr 1, 2019
Deposit Date Jan 18, 2019
Publicly Available Date Jan 18, 2019
Journal Journal of Medical Microbiology
Print ISSN 0022-2615
Electronic ISSN 1473-5644
Publisher Microbiology Society
Peer Reviewed Peer Reviewed
Volume 68
Issue 4
Pages 642-648
DOI https://doi.org/10.1099/jmm.0.000935
Keywords Microbiology (medical); Microbiology; General Medicine
Public URL https://nottingham-repository.worktribe.com/output/1480948
Publisher URL https://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000935