title: Tyro3 family-mediated cell entry of Ebola and Marburg viruses.
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.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimojima
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Kouki
authors.initials: K
authors.lastname: Fujioka
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Irimura
authors.forename: Steven
authors.initials: S
authors.lastname: Jones
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D029024:Marburgvirus / Q000502:physiology*; D008969:Molecular Sequence Data; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D017422:Sequence Analysis, DNA
chemical_list: D011991:Receptors, Virus; D020794:Receptor Protein-Tyrosine Kinases