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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.

Authors

William L. Irving

Paywast J. Jalal

Richard A. Urbanowicz

Emma Horncastle

Monika Pathak

Chun Goddard

Amanj Saeed

Christopher P. Mason

Jonathan K. Ball

C. Patrick McClure

Barnabas J. King

Alexander W. Tarr



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.

Journal Article Type Article
Publication Date Apr 1, 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
APA6 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
DOI https://doi.org/10.1099/jmm.0.000935
Keywords Microbiology (medical); Microbiology; General Medicine
Publisher URL https://jmm.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.000935

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