Efficacy of recombinant chimeric lectins, consisting of mannose binding lectin and L-ficolin, against influenza A viral infection in mouse model study

• Published in: Virus research 2013-12, Vol.178 (2), p.495-501
• Main Authors: Takahashi, Kazue, Moyo, Patience, Chigweshe, Lorencia, Chang, Wei-Chuan, White, Mitchel R., Hartshorn, Kevan L.
• Format: Article
• Language: English
• Subjects: animal models; Animals; antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; antiviral properties; Cell Line; cytokines; Disease Models, Animal; epithelial cells; Epithelial Cells - virology; Ficolin; Ficolins; Host response; humans; immunization; Immunologic Factors - administration & dosage; Immunologic Factors - pharmacology; Inflammation; influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype - drug effects; Innate immunity; lectins; Lectins - administration & dosage; Lectins - pharmacology; mannose; Mannose-binding lectin; Mannose-Binding Lectin - administration & dosage; Mannose-Binding Lectin - pharmacology; Mice; Mice, Inbred C57BL; Orthomyxoviridae; Orthomyxoviridae Infections - drug therapy; pandemic; Treatment Outcome; viruses
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2013.10.001

•We investigated efficacy of lectins in a mouse model of influenza A viral infection.•Inflammatory responses are important aspects of host defense mechanisms.•We provide a potentially new therapeutic agent against influenza A virus infection. Influenza A virus infection could result in fatal complications. Although immunization is the most effective prevention it is not effective to pandemic infection and is less effective or not approved for certain age groups. Some influenza virus strains have developed resistance to antiviral agents. Thus, new therapeutic agents are urgently needed. We focused on innate immune molecules, including mannose-binding lectin (MBL). In order to optimize its antiviral activities, we have previously generated three recombinant chimeric lectins (RCL), by introducing portions of L-ficolin, another innate immune lectin. Our in vitro characterizations previously selected RCL2 and RCL3 for further investigations against viruses, including influenza viruses. Here, we examined efficacy of these lectins against infection with PR8 (H1N1) influenza A virus using mouse model studies and a human tracheal epithelial cell system. Our results provide in vivo evidence that RCL3 is effective agent against influenza virus infection. The therapeutic mechanisms are in part by providing host protective responses mediated by cytokines. We conclude that RCL3 is a potential new innate immune anti-influenza virus therapeutic agent.