Bioinformatics helps identify TIM-1 as the receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus
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.
Using a bioinformatics screen, the team found clues that a protein encoded by the T-cell immunoglobulin and mucin domain 1 gene TIM-1 serves as a receptor for the Ebola virus strain Zaire ebolavirus in some cell types. Through a series of follow-up functional studies, they verified this interaction and showed that TIM-1 can also act as a cellular port of entry for another hemorrhagic-fever causing virus: Lake Victoria marburgvirus.
Because TIM-1-expressing cells seem to turn up in some tissues most vulnerable to Ebola and Marburg infection, researchers say, the findings hint that targeting TIM-1 might eventually help prevent some hemorrhagic infections, since their experiments suggest blocking the receptor prevents Ebola movement into cells expressing the receptor.
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Because TIM-1-expressing cells seem to turn up in some tissues most vulnerable to Ebola and Marburg infection, researchers say, the findings hint that targeting TIM-1 might eventually help prevent some hemorrhagic infections, since their experiments suggest blocking the receptor prevents Ebola movement into cells expressing the receptor.
Do you wish to know more?
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