Marc Johnson began his research career studying a rabies-like virus in fish. “Working with fish viruses is really cool research,” he notes, but there are just not a lot of people doing it,” and that sense of isolation was eventually too much. In search of collaboration and community, Johnson switched from fish viruses to HIV. Since then, the assistant professor in MU’s Department of Microbiology and Immunology has dedicated his research efforts to the study of these related humans viruses. He and his collaborators have made great progress in understanding how the HIV virus works in order to develop new therapeutics to combat the disease.
While scientists have developed ways to treat HIV, they have yet to develop a cure for the devastating disease because they have not been able to kill every last infected cell. “HIV has our immune system’s ‘number.’ Our immune system cannot figure out that those are infected cells and that it needs to kill them.” The protein responsible for HIV virus replication is the Gag protein. Much of Johnson’s current work is focused on understanding how Gag orchestrates this replication, as this knowledge could be used to uncover a treatment capable of triggering the immune system’s response.
Although the word “virus” has become a part of the everyday vernacular–what exactly is a retrovirus? Marc Johnson says viruses can be grouped into RNA viruses and DNA viruses. RNA viruses cause short-term diseases such as the flu and the common cold, whereas DNA viruses cause more long-term illnesses like herpes or cancer. “Retroviruses are a unique blend,” he explains. “They are like a DNA virus that can replicate with RNA strategies.” HIV is a retrovirus.
Comparing parts of the HIV virus to the parts of a military missile, Johnson explains the various components of the virus. A complete understanding of the HIV structure and life cycle will help scientists develop new treatments for the disease. “It’s pretty remarkable, and there’s clearly a lot about it that we don’t yet know,” Johnson admits. Most of his research revolves around the protein Gag.
As a graduate student in the Department of Molecular Microbiology and Immunology in MU’s School of Medicine, Brian Bostick works with professor Dongsheng Duan in the area of gene therapy. Bostick’s research seeks to develop a treatment for the most common form of muscular dystrophy, Duchenne muscular dystrophy, in which patients are missing a gene called dystrophin. Gene therapy involves the replacement or addition of a missing gene. Bostick’s research involves inserting this gene into a virus and then injecting it into an animal body. “Just by using the normal properties of how a virus works,” Bostick explains, “we can actually replace genes that are missing.”
Bostick’s research focuses specifically on the heart disease associated with Duchenne muscular dystrophy, where a gradual weakening of the muscles occurs—starting with the larger muscles—so that patients have trouble breathing by the time they are teenagers. For a long time, such respiratory problems had been the major cause of death among DMD patients, but doctors are now better able to treat the respiratory disease. Because the heart muscle also needs dystrophin to function properly, heart disease worsens as these patients live longer. Heart disease, in fact, is now a major cause of death among DMD patients, a problem that Bostick and his mentor Duan seek to address by developing a heart disease model in mice.
Bostick offers a quick tour of Duan’s laboratory, illustrating the processes involved in several research projects—from the mouse treadmill to the surgical area and where the mice are kept under observation. Delicately selecting several mice, Bostick shows examples of a normal mouse, one with MD, and another with MD undergoing gene replacement therapy. The difference, in both size and activity, between the untreated mouse and the one given gene therapy is remarkable and promising for future applications of this research.