Cathelicidins display conserved direct antiviral activity towards rhinovirus.

Sousa, Filipa Henderson; Casanova, Victor; Findlay, Fern; Stevens, Craig; Svoboda, Pavel; Pohl, Jan; Proudfoot, Lorna; Barlow, Peter G.

Abstract

Human rhinoviruses (HRVs) are the most common cause of viral respiratory tract infections, and are associated with significant morbidity and mortality in immunocompromised individuals and patients with pre-existing pulmonary conditions. The therapeutic options available are extremely limited and therefore novel therapeutics for HRV infections are of significant interest. Cathelicidins have been shown to have potent antiviral activity against a range of pathogens and are known to be key immunomodulatory mediators during infection. We therefore assessed the antiviral potential of cathelicidins from humans and other mammalian species against HRV, together with the potential for the human cathelicidin to modulate apoptotic pathways and alter cell viability during HRV infection. We demonstrate that LL-37, the porcine cathelicidin Protegrin-1, and the ovine cathelicidin SMAP-29 display potent antiviral activity towards HRV and that this activity is visible when either the virus is exposed to the peptides prior to cell infection or after cells have been infected. We further demonstrate that, in contrast to established findings with bacterial infection models, LL-37 does not induce apoptosis or necrosis in HRV-infected lung epithelial cells at physiological or superphysiological concentrations, but does reduce the metabolic activity of infected cells compared to uninfected cells treated with similar peptide concentrations. Collectively, the findings from this study demonstrate that the mechanism of action of cathelicidins against rhinovirus is by directly affecting the virus and we propose that the delivery of exogenous cathelicidins, or novel synthetic analogues, represent an exciting and novel therapeutic strategy for rhinovirus infection.

Citation

Sousa, F. H., Casanova, V., Findlay, F., Stevens, C., Svoboda, P., Pohl, J., Proudfoot, L., & Barlow, P. G. (2017). Cathelicidins display conserved direct antiviral activity towards rhinovirus. Peptides, 95, 76-83. https://doi.org/10.1016/j.peptides.2017.07.013

• Journal Article Type: Article
• Acceptance Date: Jul 24, 2017
• Online Publication Date: Jul 29, 2017
• Publication Date: 2017-09
• Deposit Date: Jul 25, 2017
• Publicly Available Date: Jul 30, 2018
• Journal: Peptides
• Print ISSN: 0196-9781
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 95
• Pages: 76-83
• DOI: https://doi.org/10.1016/j.peptides.2017.07.013
• Keywords: Cathelicidins, rhinovirus, antiviral activity,
• Public URL: http://researchrepository.napier.ac.uk/Output/966527
• Contract Date: Jul 27, 2017