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PMID:15831716
| Citation |
Chandran, K, Sullivan, NJ, Felbor, U, Whelan, SP and Cunningham, JM (2005) Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308:1643-5 |
|---|---|
| Abstract |
Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs. |
| Links |
PubMed Online version:10.1126/science.1110656 |
| Keywords |
Animals; Cathepsin B/antagonists & inhibitors; Cathepsin B/metabolism; Cathepsin L; Cathepsins/antagonists & inhibitors; Cathepsins/metabolism; Cell Line; Cells, Cultured; Cercopithecus aethiops; Cysteine Endopeptidases/metabolism; Cysteine Proteinase Inhibitors/pharmacology; Ebolavirus/metabolism; Ebolavirus/physiology; Endosomes/metabolism; Hydrogen-Ion Concentration; Mice; Vero Cells; Vesicular stomatitis Indiana virus/genetics; Vesicular stomatitis Indiana virus/physiology; Viral Envelope Proteins/metabolism; Virion/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0046718: viral entry into host cell |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0046718: viral entry into host cell |
ECO:0000315: |
P |
Fig. 1, murine CatB is an essential host factor for EboV GP-dependent entry. |
complete | ||||
| GO:0046718: viral entry into host cell |
ECO:0000315: |
P |
Fig. 1C and Fig. 1D, murine CatB is an essential host factor for EboV GP-dependent entry. |
complete | ||||
| GO:0046718: viral entry into host cell |
ECO:0000315: |
P |
Fig. 1B and Fig. 2D CatL is not required for infection, but does enhance infection when CatB is activated. |
complete | ||||
|
enables |
GO:0004197: cysteine-type endopeptidase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
| GO:0004197: cysteine-type endopeptidase activity |
ECO:0000315: |
F |
Fig. 1B and Fig. 2B |
complete | ||||
|
involved_in |
GO:0046718: viral entry into host cell |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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