title: T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus.
abstract: The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a cellular receptor for the deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified and characterized. Here, we show that T-cell Ig and mucin domain 1 (TIM-1) binds to the receptor binding domain of the Zaire Ebola virus (EBOV) glycoprotein, and ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection by 10- to 30-fold. Conversely, reduction of cell-surface expression of TIM-1 by RNAi decreased infection of highly permissive Vero cells. TIM-1 expression within the human body is broader than previously appreciated, with expression on mucosal epithelia from the trachea, cornea, and conjunctiva--tissues believed to be important during in vivo transmission of filoviruses. Recognition that TIM-1 serves as a receptor for filoviruses on these mucosal epithelial surfaces provides a mechanistic understanding of routes of entry into the human body via inhalation of aerosol particles or hand-to-eye contact. ARD5, a monoclonal antibody against the IgV domain of TIM-1, blocked EBOV binding and infection, suggesting that antibodies or small molecules directed against this cellular receptor may provide effective filovirus antivirals.
authors.affiliation: Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kondratowicz
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Lennemann
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Sinn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Davey
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Hunt
authors.forename: Sven
authors.initials: S
authors.lastname: Moller-Tank
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Paul
authors.initials: P
authors.lastname: Rennert
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.forename: Melinda
authors.initials: M
authors.lastname: Brindley
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Sandersfeld
authors.forename: Kathrina
authors.initials: K
authors.lastname: Quinn
authors.forename: Melodie
authors.initials: M
authors.lastname: Weller
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.forename: John
authors.initials: J
authors.lastname: Chiorini
authors.forename: Wendy
authors.initials: W
authors.lastname: Maury
mesh_terms: D001665:Binding Sites; D029043:Ebolavirus; D019142:Hemorrhagic Fever, Ebola; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D029024:Marburgvirus; D008562:Membrane Glycoproteins / Q000032:analysis*; D009092:Mucous Membrane / Q000737:chemistry; D011485:Protein Binding; D011991:Receptors, Virus / Q000032:analysis*
chemical_list: C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus