1. T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus.
- Author
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Kondratowicz, Andrew S., Lennemann, Nicholas J., Sinn, Patrick L., Davey, Robert A., Hunt, Catherine L., Moller-Tank, Sven, Meyerholz, David K., Rennert, Paul, Mullins, Robert F., Brindley, Melinda, Sandersfeld, Lindsay M., Quinn, Kathrina, Weller, Melodie, McCray, Jr., Paul B., Chiorini, John, and Maury, Wendy
- Subjects
T cell receptors ,CELL receptors ,IMMUNOGLOBULINS ,RECOMBINANT blood proteins ,MUCIN analysis ,EBOLA virus disease ,GENETICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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