Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus
Cathelicidins (CATHs) are host defense peptides (HDPs) that play an important role in the innate immune response against infections. Although multiple functions of cathelicidins have been described, including direct antimicrobial activity and several immunomodulatory effects on the host, relatively...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00426/full |
| _version_ | 1818251798374252544 |
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| author | Lianci Peng Wenjuan Du Melanie D. Balhuizen Henk P. Haagsman Cornelis A. M. de Haan Edwin J. A. Veldhuizen |
| author_facet | Lianci Peng Wenjuan Du Melanie D. Balhuizen Henk P. Haagsman Cornelis A. M. de Haan Edwin J. A. Veldhuizen |
| author_sort | Lianci Peng |
| collection | DOAJ |
| description | Cathelicidins (CATHs) are host defense peptides (HDPs) that play an important role in the innate immune response against infections. Although multiple functions of cathelicidins have been described, including direct antimicrobial activity and several immunomodulatory effects on the host, relatively little is known about their antiviral activity. Therefore, in vitro antiviral activity of chicken cathelicidins and the underlying mechanism was investigated in this study against different influenza A virus (IAV) strains. Our results show that chicken CATH-B1 has broad anti-IAV activity compared to other cathelicidins (CATH-1, -2, -3, LL-37, PMAP-23, and K9CATH) with an inhibition of viral infection up to 80% against three tested IAV strains (H1N1, H3N1, and H5N1). In agreement herewith, CATH-B1 affected virus-induced inflammatory cytokines expression (IFN-β, IL-1β, IL-6, and IL-8). Incubation of cells with CATH-B1 prior to or after their inoculation with virus did not reduce viral infection indicating that direct interaction of virus with the peptide was required for CATH-B1’s antiviral activity. Experiments using combined size exclusion and affinity-based separation of virus and peptide also indicated that CATH-B1 bound to viral particles. In addition, using electron microscopy, no morphological change of the virus itself was seen upon incubation with CATH-B1 but large aggregates of CATH-B1 and viral particles were observed, indicating that aggregation might be the mechanism of action reducing IAV infectivity. Neuraminidase (NA) activity assays using monovalent or multivalent substrates, indicated that CATH-B1 did not affect NA activity per se, but negatively affected the ability of virus particles to interact with multivalent receptors, presumably by interfering with hemagglutinin activity. In conclusion, our results show CATH-B1 has good antiviral activity against IAV by binding to the viral particle and thereby blocking viral entry. |
| first_indexed | 2024-12-12T16:14:00Z |
| format | Article |
| id | doaj.art-3644800c49bc4797b380a68063949500 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T16:14:00Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3644800c49bc4797b380a680639495002022-12-22T00:19:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-03-011110.3389/fmicb.2020.00426496096Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A VirusLianci Peng0Wenjuan Du1Melanie D. Balhuizen2Henk P. Haagsman3Cornelis A. M. de Haan4Edwin J. A. Veldhuizen5Department of Infectious Diseases & Immunology, Division of Molecular Host Defense, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Infectious Diseases & Immunology, Division Virology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Infectious Diseases & Immunology, Division of Molecular Host Defense, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Infectious Diseases & Immunology, Division of Molecular Host Defense, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Infectious Diseases & Immunology, Division Virology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Infectious Diseases & Immunology, Division of Molecular Host Defense, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsCathelicidins (CATHs) are host defense peptides (HDPs) that play an important role in the innate immune response against infections. Although multiple functions of cathelicidins have been described, including direct antimicrobial activity and several immunomodulatory effects on the host, relatively little is known about their antiviral activity. Therefore, in vitro antiviral activity of chicken cathelicidins and the underlying mechanism was investigated in this study against different influenza A virus (IAV) strains. Our results show that chicken CATH-B1 has broad anti-IAV activity compared to other cathelicidins (CATH-1, -2, -3, LL-37, PMAP-23, and K9CATH) with an inhibition of viral infection up to 80% against three tested IAV strains (H1N1, H3N1, and H5N1). In agreement herewith, CATH-B1 affected virus-induced inflammatory cytokines expression (IFN-β, IL-1β, IL-6, and IL-8). Incubation of cells with CATH-B1 prior to or after their inoculation with virus did not reduce viral infection indicating that direct interaction of virus with the peptide was required for CATH-B1’s antiviral activity. Experiments using combined size exclusion and affinity-based separation of virus and peptide also indicated that CATH-B1 bound to viral particles. In addition, using electron microscopy, no morphological change of the virus itself was seen upon incubation with CATH-B1 but large aggregates of CATH-B1 and viral particles were observed, indicating that aggregation might be the mechanism of action reducing IAV infectivity. Neuraminidase (NA) activity assays using monovalent or multivalent substrates, indicated that CATH-B1 did not affect NA activity per se, but negatively affected the ability of virus particles to interact with multivalent receptors, presumably by interfering with hemagglutinin activity. In conclusion, our results show CATH-B1 has good antiviral activity against IAV by binding to the viral particle and thereby blocking viral entry.https://www.frontiersin.org/article/10.3389/fmicb.2020.00426/fullhost defense peptidescathelicidinsinfluenzainnate immunityinfection |
| spellingShingle | Lianci Peng Wenjuan Du Melanie D. Balhuizen Henk P. Haagsman Cornelis A. M. de Haan Edwin J. A. Veldhuizen Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus Frontiers in Microbiology host defense peptides cathelicidins influenza innate immunity infection |
| title | Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus |
| title_full | Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus |
| title_fullStr | Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus |
| title_full_unstemmed | Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus |
| title_short | Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus |
| title_sort | antiviral activity of chicken cathelicidin b1 against influenza a virus |
| topic | host defense peptides cathelicidins influenza innate immunity infection |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.00426/full |
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