The role of the human cathelicidin LL-37 in rhinovirus infection

Henderson Sousa, Filipa

Abstract

Human rhinoviruses (HRVs) are the most common causes for symptomatic respiratory infections, and have been linked to severe respiratory conditions in children, and in immunocompromised and elderly individuals. Currently there are no specific treatments or vaccination available for HRV infections and novel antiviral therapeutics are urgently required. Cathelicidins are a well-characterized family of Host Defence Peptides (HDP) with potent antibacterial, antiviral and immunomodulatory functions. This study investigates the antiviral activity of the human cathelicidin LL-37 against human rhinovirus together with the capacity of the peptide to modulate inflammation and host cell death in rhinovirus infection. We demonstrate that LL-37 has significant antiviral activity against HRV1B when the virus is exposed to peptide prior to cell infection, and when cells are infected prior to LL-37 treatment, indicating that LL-37 exerts its effects by directly targeting the virus and/or acting on host cells reducing their susceptibility to infection. Cathelicidin-mediated inflammatory pathway modulation was measured via quantification of IL-8, IL-6 and CCL5 gene expression and protein release. Our data indicates that LL-37 can significantly reduce pro-inflammatory gene expression and protein release induced by HRV1B infection in bronchial epithelial cells, when the peptide is exposed to HRV prior to infection. However, LL-37 was shown to increase HRV-induced inflammatory gene expression and protein release by bronchial epithelial cells, when cells were infected prior to LL-37 treatment. This data indicates that the cellular microenvironment and the context of cathelicidin exposure could determine the direction of cellular response to infection. We further demonstrate that LL-37 suppresses induction of apoptotic cell death in HRV-infected cells, which may represent a novel immunomodulatory role for LL-37 in the context of this infection. Taken collectively, these data suggest that cathelicidins represent an exciting therapeutic avenue for rhinovirus infections, via targeting of virus particles and modulation of host cell responses to infection.

Citation

Henderson Sousa, F. The role of the human cathelicidin LL-37 in rhinovirus infection. (Thesis). Edinburgh Napier University. Retrieved from http://researchrepository.napier.ac.uk/Output/2070903

• Thesis Type: Thesis
• Deposit Date: Aug 21, 2019
• Publicly Available Date: Aug 29, 2019
• Keywords: human rhinoviruses; antiviral therapeutics; cathelicidins; host defence peptides; inflammation; infection; host cell responses
• Public URL: http://researchrepository.napier.ac.uk/Output/2070903
• Award Date: Jul 4, 2019