This study, led by senior author Dr Paul Bates, an associate professor in the Department of Microbiology, also demonstrated a new mechanism for how viral proteins are activated within host cells.
To gain entry, a virus binds to receptors on the surface of the host cell, and is taken up into a vesicle, or sphere, inside the cell. Unlike most known viruses, the SARS (severe acute respiratory syndrome) coronavirus (like the Ebola virus) needs one more step to infect the cell. The proteins within the membrane of both SARS and Ebola need to be cut by special cellular enzymes (cathepsins) in order to replicate within the host cell.
“This paper changes the thinking of the field,” said Bates. “Up to this point, everyone thought all of the activation steps were at the cell surface or due to the low pH environment in the vesicle. Our paper shows that it’s not just low pH, but the cathepsin proteases in the vesicles that clip the viral protein. This gives us a new target to address in the development of therapeutics against the SARS virus.”
The researchers found that several chemical inhibitors of cathepsin activity blocked infection of human cell lines by the SARS virus. The findings have led to a better understanding that the cutting of viral protein by cathepsins is necessary for infectivity and is likely not unique because both the SARS and Ebola viruses are now known to use a similar mechanism to invade their host cells.
If these proteases are important for other viruses, they represent a new way to stop viral infection.