title: Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses.
abstract: The collectins have been shown to have a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e.g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum, but also in respiratory secretions; however, there has been little study of the role of ficolins in viral infection. In this study, we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are generally not inhibited by the collectins surfactant protein D or mannose binding lectin because of a paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Anamika
authors.initials: A
authors.lastname: Verma
authors.forename: Mitchell
authors.initials: M
authors.lastname: White
authors.forename: Vinod
authors.initials: V
authors.lastname: Vathipadiekal
authors.forename: Shweta
authors.initials: S
authors.lastname: Tripathi
authors.forename: Julvet
authors.initials: J
authors.lastname: Mbianda
authors.forename: Micheal
authors.initials: M
authors.lastname: Ieong
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003168:Complement Fixation Tests; D004285:Dogs; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D037102:Lectins / Q000502:physiology*; D051379:Mice; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D058873:Pandemics; D012621:Seasons; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; D014763:Viral Matrix Proteins