T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus
| Autor: | Paul B. McCray, Kathrina Quinn, Patrick L. Sinn, Robert A. Davey, David K. Meyerholz, Andrew S. Kondratowicz, Wendy Maury, Sven Moller-Tank, Robert F. Mullins, Lindsay M Sandersfeld, Melodie L. Weller, Paul D. Rennert, Melinda A. Brindley, John A. Chiorini, Nicholas J. Lennemann, Catherine L. Hunt |
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| Rok vydání: | 2011 |
| Předmět: |
Zaire ebolavirus
T cell medicine.disease_cause Hepatitis A Virus Cellular Receptor 1 Viral envelope medicine Humans Receptor Ebolavirus Multidisciplinary Binding Sites Membrane Glycoproteins Mucous Membrane biology Biological Sciences Hemorrhagic Fever Ebola Marburgvirus biology.organism_classification Virology medicine.anatomical_structure Vero cell Receptors Virus Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1019030108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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