Scientists at the U.S. Department of Energys Brookhaven National Laboratory and their collaborators have discovered that some viruses can use the most abundant protein in the cells they are infecting to destroy the cells and allow new viruses to escape to infect others. The findings, described in the November 29, 2002, issue of the Journal of Biological Chemistry, build upon earlier Brookhaven research on how virus particles become infectious (see related story) and may lead to the design of more effective antiviral remedies.
This ribbon diagram is a theoretical representation of the structure of adenovirus protease (red) bound to the cytoskeleton protein actin (green). The blue, green, and yellow balls show the location of the active site of the adenovirus protease.
The same two cells were photographed to show the location of the adenovirus protease (labeled with a green fluorescent molecule) and the cytoskeleton protein cytokeratin 18 (labeled with a red fluorescent molecule). The adenovirus protease is known to cleave cytokeratin 18 (as well as other cytoskeletal proteins), and this experiment shows they are located at the same sites within the cells.
"This is a new and philosophically interesting way for a virus to escape from cells," said Brookhaven biologist Walter Mangel, a coauthor on the paper. "In essence, a protein in the infected cells can serve as the seed of the cells’ own destruction."
Mangels group has previously shown that adenovirus -- a virus that causes respiratory and gastrointestinal infections and also conjunctivitis -- produces a protein-cleaving enzyme, or protease, to complete the maturation of newly synthesized virus particles. Similar to the way supportive scaffolding is removed after the completion of a construction project, this protease cleaves, or cuts out, viral "construction" proteins, leaving infectious virus particles behind.
Karen McNulty Walsh, | Brookhaven National Laboratory
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