T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire ebolavirus and Lake Victoria marburgvirus

Academic Article

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.
  • Digital Object Identifier (doi)

    Author List

  • Kondratowicz AS; Lennemann NJ; Sinn PL; Davey RA; Hunt CL; Moller-Tank S; Meyerholz DK; Rennert P; Mullins RF; Brindley M
  • Start Page

  • 8426
  • End Page

  • 8431
  • Volume

  • 108
  • Issue

  • 20