PMID:20202662

Citation	Bhattacharyya, S, Warfield, KL, Ruthel, G, Bavari, S, Aman, MJ and Hope, TJ (2010) Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401:18-28
Abstract	Ebola virus (EBOV) infects several cell types and while viral entry is known to be pH-dependent, the exact entry pathway(s) remains unknown. To gain insights into EBOV entry, the role of several inhibitors of clathrin-mediated endocytosis in blocking infection mediated by HIV pseudotyped with the EBOV envelope glycoprotein (EbGP) was examined. Wild type HIV and envelope-minus HIV pseudotyped with Vesicular Stomatitis Virus glycoprotein (VSVg) were used as controls to assess cell viability after inhibiting clathrin pathway. Inhibition of clathrin pathway using dominant-negative Eps15, siRNA-mediated knockdown of clathrin heavy chain, chlorpromazine and sucrose blocked EbGP pseudotyped HIV infection. Also, both chlorpromazine and Bafilomycin A1 inhibited entry of infectious EBOV. Sensitivity of EbGP pseudotyped HIV as well as infectious EBOV to inhibitors of clathrin suggests that EBOV uses clathrin-mediated endocytosis as an entry pathway. Furthermore, since chlorpromazine inhibits EBOV infection, novel therapeutic modalities could be designed based on this lead compound.
Links	PubMed Online version:10.1016/j.virol.2010.02.015
Keywords	Animals; Cell Line; Chlorpromazine/pharmacology; Clathrin/metabolism; Ebolavirus/physiology; Hemorrhagic Fever, Ebola/virology; Humans; Viral Envelope Proteins/metabolism; Virus Internalization
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TFR1	part_of	GO:0048471: perinuclear region of cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TFR1		GO:0048471: perinuclear region of cytoplasm	ECO:0000314:		C		Fig. 2C	complete CACAO 2403
HUMAN:TRFE	part_of	GO:0048471: perinuclear region of cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TRFE		GO:0048471: perinuclear region of cytoplasm	ECO:0000314:		C		Fig. 2B	complete CACAO 2404
EBOZM:VGP	involved_in	GO:0046718: viral entry into host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
EBOZM:VGP	part_of	GO:0030430: host cell cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
EBOZM:VGP		GO:0030430: host cell cytoplasm	ECO:0000314:		C		Fig. 2	complete CACAO 2405
EBOZM:VGP		GO:0046718: entry of virus into host cell	ECO:0000315:		P		Fig. 5C	complete CACAO 2406
HUMAN:EPS15		GO:0046718: entry of virus into host cell	ECO:0000315:		P		Fig. 4B and Fig. 4C	complete CACAO 2407
HUMAN:EPS15	involved_in	GO:0046718: viral entry into host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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