Journal article
T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus
Proceedings of the National Academy of Sciences - PNAS, Vol.108(20), pp.8426-8431
05/17/2011
DOI: 10.1073/pnas.1019030108
PMCID: PMC3100998
PMID: 21536871
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.
Details
- Title: Subtitle
- T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus
- Creators
- Andrew S Kondratowicz - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USANicholas J LennemannPatrick L SinnRobert A DaveyCatherine L HuntSven Moller-TankDavid K MeyerholzPaul RennertRobert F MullinsMelinda BrindleyLindsay M SandersfeldKathrina QuinnMelodie WellerPaul B McCray JrJohn ChioriniWendy Maury
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(20), pp.8426-8431
- DOI
- 10.1073/pnas.1019030108
- PMID
- 21536871
- PMCID
- PMC3100998
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- HL075363 / NHLBI NIH HHS U54 AI057156 / NIAID NIH HHS R01 AI063513 / NIAID NIH HHS AI063513 / NIAID NIH HHS T32 AI 007533-12 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R56 AI063513 / NIAID NIH HHS AI057156 / NIAID NIH HHS Intramural NIH HHS R21 AI064526 / NIAID NIH HHS R01 HL075363 / NHLBI NIH HHS R01 AI077519 / NIAID NIH HHS R21 AI082409 / NIAID NIH HHS AI064526 / NIAID NIH HHS R21 AI073330 / NIAID NIH HHS CA086862 / NCI NIH HHS DK054759 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS AI073330 / NIAID NIH HHS AI082409 / NIAID NIH HHS DK54759 / NIDDK NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 05/17/2011
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980094202771
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