title: Efficacy of recombinant chimeric lectins, consisting of mannose binding lectin and L-ficolin, against influenza A viral infection in mouse model study.
abstract: 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.
authors.affiliation: Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ktakahashi1@partners.org.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Patience
authors.initials: P
authors.lastname: Moyo
authors.forename: Lorencia
authors.initials: L
authors.lastname: Chigweshe
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chang
authors.forename: Mitchel R
authors.initials: MR
authors.lastname: White
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D037102:Lectins / Q000008:administration & dosage* / Q000494:pharmacology; D037601:Mannose-Binding Lectin / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D016896:Treatment Outcome; D000097604:Ficolins
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins
keywords: Ficolin; Host response; Inflammation; Influenza A virus; Innate immunity; Mannose-binding lectin