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.

doi:10.1099/jmm.0.000935

Authors

WILLIAM IRVING will.irving@nottingham.ac.uk
Professor of Virology

Paywast J. Jalal

Richard A. Urbanowicz

Emma Horncastle

MONIKA PATHAK m.pathak@nottingham.ac.uk
Research Fellow

Chun Goddard

Amanj Saeed

Christopher P. Mason

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

PATRICK MCCLURE patrick.mcclure@nottingham.ac.uk
Senior Research Fellow

Barnabas J. King

ALEXANDER TARR alex.tarr@nottingham.ac.uk
Assistant Professor

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