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Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.
Persson, B David; John, Lijo; Rafie, Karim; Strebl, Michael; Frängsmyr, Lars; Ballmann, Monika Z; Mindler, Katja; Havenga, Menzo; Lemckert, Angelique; Stehle, Thilo; Carlson, Lars-Anders; Arnberg, Niklas.
Afiliação
  • Persson BD; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • John L; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Rafie K; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • Strebl M; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Frängsmyr L; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Ballmann MZ; Wallenberg Centre for Molecular Medicine, Umeå University, SE-90187 Umeå, Sweden.
  • Mindler K; Department of Medical Biochemistry, Umeå University, SE-90187 Umeå, Sweden.
  • Havenga M; Interfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.
  • Lemckert A; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • Stehle T; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Carlson LA; Batavia Biosciences, 2333 CL Leiden, The Netherlands.
  • Arnberg N; Interfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33384338
ABSTRACT
Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Regulação Viral da Expressão Gênica / Adenovírus Humanos / Proteínas do Capsídeo / Internalização do Vírus Limite: Humanos Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: Suécia

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Regulação Viral da Expressão Gênica / Adenovírus Humanos / Proteínas do Capsídeo / Internalização do Vírus Limite: Humanos Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: Suécia