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RESEARCHERS FIND CLUES TO MYSTERY OF AIDS VIRUS
19 November 2000 - University of Wisconsin-Madison
| Scientists working with monkeys at the University of Wisconsin-Madison have discovered new evidence explaining why retroviruses such as HIV in people and SIV in rhesus monkeys are so variable and difficult for the body's immune system to target and kill. |
The finding, reported in the November issue of the scientific journal Nature Medicine, is another step toward the development of effective vaccines to prevent AIDS. David I. Watkins, professor of pathology and laboratory medicine, and two graduate students, David Evans and David O'Connor, conducted the research at the Wisconsin Regional Primate Research Center, one of eight U.S. primate centers supported by the National Institutes of Health. A key finding: Killer cells called cytotoxic T lymphocyte cells likely play a greater role than previously thought in controlling infection in both humans and monkeys, says Watkins. "Two important arms of the immune system that respond to infection are CTLs and antibodies," Watkins explains. "However, the antibody response does not fully develop until much later. By contrast, the peak of the CTL response coincides with early control of virus replication." Within a month after infection, he says, enormous replication takes place. The virus infects and then copies itself within host cells, turning the host cells into "virus factories." CTLs recognize these infected cells and destroy them, limiting viral spread. Unfortunately, although a strong CTL response arises early, it ultimately fails to prevent progression to AIDS. Previous research has implied that HIV escapes the CTL response by replacing specific amino acids within regions of its own proteins that would normally be recognized by CTLs. The researchers tracked 10 of these regions, called epitopes, during the course of disease progression in rhesus monkeys. All 10 epitopes accumulated amino acid replacements. Many of the replacements either reduced or eliminated the CTLs' ability to kill virus-infected cells. "This supports the CTL escape hypothesis and underscores the importance of these killer cells in controlling viral replication," Watkins says. Further characterization of CTLs and the epitopes they recognize is critical to designing effective vaccines, he added. The Wisconsin Regional Primate Research Center is now developing a colony of genetically defined rhesus monkeys for more controlled AIDS research. The Nature Medicine study represents collaboration between Watkins and Alessandro Sette at Epimune, Inc., of San Diego, Calif. The work also involved the Laboratory of Genetics and Department of Pathology and Laboratory Medicine at UW-Madison, Biomedical Primate Research Centre-TNO in the Netherlands, and the Institute of Molecular Evolutionary Genetics at Pennsylvania State University.
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About: University of Wisconsin-Madison
In achievement and prestige, the University of Wisconsin-Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW-Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Many of its programs are hailed as world leaders in instruction, research and public service.The university traces its roots to a clause in the Wisconsin Constitution, which decreed that the state should have a prominent public university. In 1848, Nelson Dewey, Wisconsin’s first governor, signed the act that formally created the university, and its first class, with 17 students, met in a Madison school building on February 5, 1849. From those humble beginnings, the university has grown into a large, diverse community, with about 40,000 students enrolled each year. These students represent every state in the nation, as well as countries from around the globe, making for a truly international population. UW-Madison is the oldest and largest campus in the University of Wisconsin System, a statewide network of 13 comprehensive universities, 13 freshman-sophomore transfer colleges and an extension service. One of two doctorate-granting universities in the system, UW-Madison’s specific mission is to provide "a learning environment in which faculty, staff and students can discover, examine critically, preserve and transmit the knowledge, wisdom and values that will help insure the survival of this and future generations and improve the quality of life for all." The university achieves these ends through innovative programs of research, teaching and public service. Throughout its history, UW-Madison has sought to bring the power of learning into the daily lives of its students through innovations such as residential learning communities and service-learning opportunities. Students also participate freely in research, which has led to life-improving inventions from more fuel-efficient engines to cutting-edge genetic therapies. Students, faculty and staff are motivated by a tradition known as the "Wisconsin Idea," described by UW President Charles Van Hise in 1904 as the compelling need to carry "the beneficent influence of the university ... to every home in the state." The Wisconsin Idea permeates the university’s work and helps forge close working relationships among university faculty and students and the state’s industries and government. |
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