Glycosylation of Human IgA Directly Inhibits Influenza A and Other Sialic-Acid-Binding Viruses
Michael A. Maurer,
Larissa Meyer,
Matteo Bianchi,
Hannah L. Turner,
Ngoc P.L. Le,
Marco Steck,
Arkadiusz Wyrzucki,
Vanessa Orlowski,
Andrew B. Ward,
Max Crispin,
Lars Hangartner
Affiliations
Michael A. Maurer
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Larissa Meyer
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Matteo Bianchi
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Hannah L. Turner
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, U.S.A
Ngoc P.L. Le
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Marco Steck
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Arkadiusz Wyrzucki
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Vanessa Orlowski
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Andrew B. Ward
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, U.S.A
Max Crispin
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Center for Biological Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK; Institute for Life Sciences, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK
Lars Hangartner
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Corresponding author
Summary: Immunoglobulin A (IgA) plays an important role in protecting our mucosal surfaces from viral infection, in maintaining a balance with the commensal bacterial flora, and in extending maternal immunity via breast feeding. Here, we report an additional innate immune effector function of human IgA molecules in that we demonstrate that the C-terminal tail unique to IgA molecules interferes with cell-surface attachment of influenza A and other enveloped viruses that use sialic acid as a receptor. This antiviral activity is mediated by sialic acid found in the complex N-linked glycans at position 459. Antiviral activity was observed even in the absence of classical antibody binding via the antigen binding sites. Our data, therefore, show that the C-terminal tail of IgA subtypes provides an innate line of defense against viruses that use sialic acid as a receptor and the role of neuraminidases present on these virions. : Vertebrate IgA molecules possess a conserved N-linked glycosylated C-terminal tail. Maurer et al. show that sialic acid found in the complex glycosylation of the C-terminal tail of human IgA1 inhibits sialic-acid-binding viruses and, therefore, may constitute an additional line of innate immunity. Keywords: immunoglobulin, antibodies, IgA, glycosylation, virus neutralization, innate immunity, influenza virus, heterosubtypic antibodies, mucosal immunity, neuraminidase
