Cathelicidins display conserved direct antiviral activity towards rhinovirus
| العنوان: | Cathelicidins display conserved direct antiviral activity towards rhinovirus |
|---|---|
| المؤلفون: | Victor Casanova, Jan Pohl, Peter G. Barlow, Filipa Henderson Sousa, Fern Findlay, Pavel Svoboda, Craig Stevens, Lorna Proudfoot |
| المصدر: | Peptides |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Biomedical Science Research Group, Rhinovirus, Physiology, Swine, medicine.medical_treatment, Cell, Biology, medicine.disease_cause, Biochemistry, Antiviral Agents, Virus, Centre for Nano Safety, Cathelicidin, Microbiology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, 616 Diseases, Cathelicidins, medicine, Animals, Humans, Microbiology Research Group, Viability assay, QR180 Immunology, Respiratory Tract Infections, Sheep, Respiratory tract infections, LL-37, Epithelial Cells, Blood Proteins, Immunology and infection, 030104 developmental biology, medicine.anatomical_structure, Cathelicidins, rhinovirus, antiviral activity, Apoptosis, Health, 030220 oncology & carcinogenesis, Immunology, Respiratory, lipids (amino acids, peptides, and proteins), Infection, Antimicrobial Cationic Peptides, Research Paper |
| الوصف: | Highlights • The host defence peptide LL-37 can reduce Human Rhinovirus 1B (HRV1B) replication in airway epithelial cells. • The antiviral activity of LL-37 is sequence specific. • LL-37 reduces the metabolic activity of cells infected with HRV1B without inducing substantial apoptotic or necrotic cell death. • The antiviral activity of cathelicidin peptides towards HRV1B is conserved in peptides from other mammalian species including pig and sheep. 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. |
| وصف الملف: | |
| تدمد: | 1873-5169 0196-9781 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::87858345af0baf1b99f380dc4741b069Test https://pubmed.ncbi.nlm.nih.gov/28764966Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....87858345af0baf1b99f380dc4741b069 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18735169 01969781 |
|---|