How Some Cancers Infect Cells - research findings - Brief Article

USA Today (Society for the Advancement of Education), Oct, 2000

Researchers at Purdue University, West Lafayette, Ind., have identified the role of a protein segment that allows some cancer-causing viruses to latch onto and infect cells. Analysis of the protein segment--which bears a striking resemblance to bee venom--may increase scientists' understanding of how retroviruses and some other viruses enter cells. The work may lead to new therapies aimed at thwarting such viruses. (Retroviruses can cause tumors and leukemia in animals and humans. The AIDS virus is a retrovirus.)

"The new data have important implications not only for the membrane fusion processes that lead to the entry of retroviruses and other viruses such as influenza viruses and the Ebola virus, but also to normal cellular processes such as fertilization of an egg by a sperm," notes David Sanders, an assistant professor in the Department of Biological Sciences.

Working with doctoral student Gwen Taylor, he discovered the importance of an amino acid sequence which is part of a protein that was previously thought to be unassuming. Their study shows this segment of the protein is essential for membrane fusion, and that changing just one amino acid in the sequence could eliminate fusion between the virus and its host. The findings may lead to novel treatments to block the entry of retroviruses and other membrane-possessing viruses.

The proteins that stud the membrane surrounding a retrovirus--called envelope proteins--allow the virus to bind to a host cell and promote the fusion of the virus and cell membranes. It is through this fusion process that the virus enters the cell. Although the process of cell fusion has long been recognized, the structure of these membrane-spanning proteins include regions that were poorly understood, Sanders explains. "The specific amino-acid sequence of these regions, for example, was not considered critical for viral fusion because, in looking across all the different types of viruses, there is a tremendous amount of variety in this region, indicating that the amino-acid sequence may be random."

Looking at a family of retroviruses that includes feline and human T-cell leukemia viruses, however, he found that the membrane-spanning domain was not random, and in fact shared similarities with some other types of viruses. Using the Moloney murine leukemia virus as a model, Sanders and Taylor showed that, by replacing part of the sequence, they could eliminate membrane fusion, while having no effect on any other known function of the protein.

Their analysis of the protein also showed that the amino acid sequence in this region shares some important characteristics with the active agent of bee venom, which works by forming holes in membranes. "This is exactly what the bee venom and some other toxins look like," Sanders points out. "And the way they work is to form a pore, or hole, in the membrane." The findings suggest that this region of the retrovirus envelope protein may be forming a similar hole in the membrane of the host cell during the fusion process. These insights may point scientists toward new ways of thwarting viruses and help redefine scientific models of how membrane fusion occurs, Sanders predicts.