Ebola virus uses clathrin-mediated endocytosis as an entry pathway

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 wi...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-05, Vol.401 (1), p.18-28
Main Authors: Bhattacharyya, Suchita, Warfield, Kelly L, Ruthel, Gordon, Bavari, Sina, Aman, M. Javad, Hope, Thomas J
Format: Article
Language:English
Subjects:
Animals
Cell Line
Chlorpromazine
Chlorpromazine - pharmacology
Clathrin - metabolism
Clathrin endocytic pathway
Ebola virus
Ebolavirus - physiology
Entry
Eps15
Hemorrhagic Fever, Ebola - virology
Human immunodeficiency virus
Humans
Infectious Disease
Sucrose
Vesicular stomatitis virus
Viral Envelope Proteins - metabolism
Virus Internalization
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2010.02.015