Ebola virus uses clathrin-mediated endocytosis as an entry pathway.
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.
Bhattacharyya
Suchita
S
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Warfield
Kelly L
KL
Ruthel
Gordon
G
Bavari
Sina
S
Aman
M Javad
MJ
Hope
Thomas J
TJ
D000818:Animals; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism*; D029043:Ebolavirus / Q000502:physiology*; D019142:Hemorrhagic Fever, Ebola / Q000821:virology*; D006801:Humans; D014759:Viral Envelope Proteins / Q000378:metabolism; D053586:Virus Internalization
D002966:Clathrin; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D002746:Chlorpromazine