PMID:21536871

Citation	Kondratowicz, AS, Lennemann, NJ, Sinn, PL, Davey, RA, Hunt, CL, Moller-Tank, S, Meyerholz, DK, Rennert, P, Mullins, RF, Brindley, M, Sandersfeld, LM, Quinn, K, Weller, M, McCray, PB Jr, Chiorini, J and Maury, W (2011) T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proc. Natl. Acad. Sci. U.S.A. 108:8426-31
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.
Links	PubMed PMC3100998 Online version:10.1073/pnas.1019030108
Keywords	Binding Sites; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburgvirus; Membrane Glycoproteins/analysis; Mucous Membrane/chemistry; Protein Binding; Receptors, Virus/analysis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CHLAE:HAVR1		GO:0001618: viral receptor activity	ECO:0000315:		F		Fig. 2A and Fig. 4(B,C,D)	complete CACAO 2169
CHLAE:HAVR1		GO:0031514: motile cilium	ECO:0000314:		C		Fig. 3E	complete CACAO 2212
CHLAE:HAVR1	enables	GO:0001618: virus receptor activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
CHLAE:HAVR1	part_of	GO:0031514: motile cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:HAVR1	part_of	GO:0031514: motile cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:HAVR1	enables	GO:0001618: virus receptor activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:HAVR1		GO:0001618: viral receptor activity	ECO:0000314:		F		Fig. 2 (Except A), and Fig. 4E	complete CACAO 2170
HUMAN:HAVR1		GO:0031514: motile cilium	ECO:0000314:		C		Fig. 3A and Fig. 3F	complete CACAO 2209

References

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