(PHILADELPHIA - December 2, 2004) - Scientists at The Wistar Institute, working in collaboration with colleagues at the University of Helsinki, have discovered structural similarities among viruses that infect hosts from all three domains of life. These structural similarities suggest that the viruses, despite their genomic variations and differences in hosts, may have evolved from a common ancestor billions of years ago. The findings will be published in the December 3 issue of Molecular Cell.

Until recently, scientists have tended to view the viral universe as unrelated families of viruses, with little attention given to their similarities. "People tended to concentrate on a single type of virus," says Roger M. Burnett, Ph.D., senior author of the study and professor in Wistar's immunology program. "It hadn't been appreciated until a few years ago that there are great structural similarities among seemingly unrelated viruses."

The research builds on earlier work by Burnett and his colleagues, in which they determined the structure of a virus called PRD1 that infects bacteria.  They found that it has remarkable structural similarities to human adenoviruses, which cause various diseases, including respiratory infections. Using data from their own and other laboratories, the researchers have created structure-based models to demonstrate structural similarities in the coats - proteins and architecture - among viruses that infect hosts from all three domains of life. The three domains are eukarya (animals, plants, and other higher order organisms); bacteria; and archaea (a recently described group of microorganisms that differ from bacteria and are commonly found in extreme environments like geysers, and alkaline, acidic or salty waters).

It is difficult to study viral evolution, Burnett says, because viruses live symbiotically with their hosts and adopt host-related traits. Instead of being inherited from a viral ancestor, these host-related traits may be picked up from the host or other microorganisms. For viruses that diverged from a common ancestor billions of years ago, and so have significant differences in genome size, genetic complexity, and host, structural similarities may be the only evidence remaining that indicates a shared lineage.

While viral lineage is in itself a question that interests scientists, research in this area may ultimately inform anti-viral drug discovery. Structural similarities in viruses may point to sites of enzymatic activity that could be targeted with drugs. For example, in two of the viruses studied, one vertex of the apparently symmetric coat is different and used for DNA packaging. With this knowledge in mind, researchers could explore whether human viruses with similar coat proteins also have a unique vertex devoted for DNA packaging.  If so, new anti-virals could be developed to target this mechanism.

In addition to senior author Burnett, the other authors of the study are: Stacy D. Benson, Ph.D., formerly of Wistar and now an assistant professor of chemistry at Oklahoma State University, and Jaana K.H. Bamford, Ph.D., and Dennis H. Bamford, Ph.D., both of the University of Helsinki.

Funding for the research was provided by the National Institutes of Health; the Human Frontiers Science Program; the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health; and the Academy of Finland.  

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center - one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.

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