Reuben Harris, professor in the University of Minnesota's College of Biological Sciences, has been awarded a five-year, $10 million grant from the National Institutes of Health to direct a large-scale research effort to study a human antiviral protein with potential for treating HIV and other viral diseases.
The goal of the study will be to produce atomic resolution images of the protein (APOBEC3G) to better understand how it interacts with other proteins in human cells and with HIV to prevent the virus from attaching to and entering cells. This fundamental knowledge could lead to novel methods to alter this protein to make it more effective.
"You have to understand the nuts and bolts of the system before you can make alterations to interfere with the process," says Harris, an associate professor of biochemistry, molecular biology and biophysics. "I'm very optimistic that this will research will enable us to use this novel protein against HIV and other diseases."
The approach represents a paradigm shift in treating viral diseases. While most other strategies focus on the virus itself, this is among the first to focus on the host.
"Conventional methods focusing on HIV are susceptible to the inevitable emergence of drug resistant virus isolates, whereas drugs that target stable cellular proteins may be much less prone to this problem" says Harris.
Human cells produce a family of antiviral proteins (called APOBECs) that have the ability to destroy HIV. But HIV has evolved a way to overcome them using an accessory protein called Vif (virion infectivity factor) to degrade the APOBEC proteins and allow the virus to spread. In a previous study, researchers in Harris's lab showed how HIV binds to and destroys one of the APOBEC proteins. This suggests that a simple change in the chemical structure of the APOBEC proteins could convert the human proteins to more effective antiviral agents. A better understanding of the interaction at molecular and atomic levels is needed to move in that direction.
Harris will lead five teams with complementary skills in molecular virology, NMR spectroscopy, X-ray crystallography, biophysics and biochemistry. Matsuo Hiroshi, associate professor in the College of Biological Sciences, is also a project leader, and Joachim Mueller, associate professor in the College of Science and Engineering's Department of Physics, is a key interdepartmental collaborator. Other sites include the University of Massachusetts Medical School, University of Nebraska and Hebrew University in Israel. Funded by the National Institute of General Medical Sciences, this Program Project grant will support training opportunities for students while advancing research. About half of the projected full amount of the $10 million grant will remain at the University of Minnesota.
|Contact: Jeff Falk|
University of Minnesota