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.

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., Saeed, A., Mason, C. P., Ball, J. K., McClure, C. P., King, B. J., & 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
• Contract Date: Jan 18, 2019