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Scientists reveal a new way viruses cause cells to self-destruct

UPTON, NY -- Scientists at the U.S. Department of Energy's 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 http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr120401.htm) and may lead to the design of more effective antiviral remedies.

"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."

Mangel's 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.

This viral protease is produced in the cytoplasm in an inactive form, and must migrate to the nucleus to become activated in newly synthesized viral particles by two viral cofactors. Once activated, it can cleave several viral proteins to complete the viral maturation process. There were no indications that the protease could be activated in the cell's cytoplasm.

When Mangel presented this research at a seminar at Princeton University, Clarence Schutt, a Princeton chemistry professor, pointed out that the amino acid sequence of one of the viral cofactors was dramatically similar to
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
19-Nov-2002


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