Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection
Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection
Science, Vol. 308, 1643-1645, 2005
Speaker：Jung-yen Liu Time：2005/09/28
Commentator：Chun-hua Chen Place：Room 601
Abstract：
Ebola virus（EboV）is an emerging human pathogen responsible for outbreaks of highly mortality hemorrhagic fever syndromes. The structure of EboV GP, which mediates viral entry into target cells by membrane fusion, is analogous with the envelope glycoproteins of HIV and influenza virus：It’s a trimerof disulphide-linked heterodimers in which the membrane distal subunit GP1 regulates the fusion activity of the transmembrane subunit GP2. From studies of HIV and influenza virus, we know that infection by these viruses need a specific signal. However, the triggering signal for EboV is not identified so far. Chandran et al found VSV particles bearing EboV GP（VSV-GP）infection is inhibited by an inhibitor of Cathepsin B（CatB）, an endosomal cysteine protease. Furthermore, they observed EboV GP1 is cleaved to form about 18-kD N-terminal fragment （GP118K）by purified CatB or related enzyme, CatL, and GP118K-containing VSV particles are still infectious by depending on CatB. These findings suggest GP118K needs a downstream CatB-dependent step.They further demonstrated that further digestion of GP118K by CatB inactivates VSV particles infection via releasing the remainder GP118K and inducing premature membrane fusion machinery. In conclusion, this paper indicates that GP proteolysis by CatB provides a triggering signal for EboV infection and is functionally equivalent to receptor binding for HIV. With no effective treatment for EboV infection, the investigation of the role of CatB may provides a newdirection in the treatment of this infection.
References：
1. W. Weissenhorn, A. Carfi, K. H. Lee, et al. Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol. Cell 2, 605, 1998.
2. K. Chandran, N. J. Sullivan, U. Felbor, et al. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science 308, 1643, 2005.