Tyro3 family-mediated cell entry of Ebola and Marburg viruses

Masayuki Shimojima, Ayato Takada, Hideki Ebihara, Gabriele Neumann, Kouki Fujioka, Tatsuro Irimura, Steven Jones, Heinz Feldmann, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and Mer-in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection.

Original languageEnglish (US)
Pages (from-to)10109-10116
Number of pages8
JournalJournal of virology
Volume80
Issue number20
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Shimojima, M., Takada, A., Ebihara, H., Neumann, G., Fujioka, K., Irimura, T., Jones, S., Feldmann, H., & Kawaoka, Y. (2006). Tyro3 family-mediated cell entry of Ebola and Marburg viruses. Journal of virology, 80(20), 10109-10116. https://doi.org/10.1128/JVI.01157-06