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Jens Christian Jensenius

Human H-ficolin inhibits replication of seasonal and pandemic influenza A viruses

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  • Anamika Verma
  • ,
  • Mitchell White
  • ,
  • Vinod Vathipadiekal
  • ,
  • Shweta Tripathi
  • ,
  • Julvet Mbianda
  • ,
  • Micheal Ieong
  • ,
  • Li Qi
  • ,
  • Jeffery K Taubenberger
  • ,
  • Kazue Takahashi
  • ,
  • Jens C Jensenius
  • Steffen Thiel
  • Kevan L Hartshorn
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.
Original languageEnglish
JournalJournal of Immunology
Volume189
Issue5
Pages (from-to)2478-87
Number of pages10
ISSN0022-1767
DOIs
Publication statusPublished - 2012

    Research areas

  • Animals, Antiviral Agents, Cell Line, Tumor, Cells, Cultured, Complement Fixation Tests, Dogs, Glycoproteins, Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza, Human, Lectins, Mice, Neutralization Tests, Orthomyxoviridae Infections, Pandemics, Seasons, Viral Matrix Proteins, Virus Replication

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