Identification of Mechanism of Infection may Lead to Better Treatment and Prevention
Infection from the chikungunya virus typically provokes joint pain and fever lasting about 1 week. But in up to 50% of cases, the infection progresses to a persistent form of arthritis that can continue for months or years. No effective treatments or vaccines currently exist for arthritogenic alphaviruses such as chikungunya, with care limited to symptom management via rest, fluids, and OTC analgesics. But new research from Washington University School of Medicine has isolated the mechanism by which the chikungunya and related viruses infect cells, and the finding could lead to the development of new avenues of treatment or prevention. Senior author Michael Diamond, MD, PhD, commented, “We now know how chikungunya gets into cells, and we may have found a way to block the infection. If the virus cannot get into the cell, it is unable to replicate and cause infection and disease.” The findings were published earlier this week in the Nature.
Chikungunya and related viruses are transmitted by infected mosquitos, and constitute a growing threat to more regions of the world. Once found only in Africa and Asia, an outbreak beginning in 2013 has infected over 1 million people in the Caribbean and South America. Working with mouse models, the Washington University team isolated a specific protein, Mxra8, that the virus uses as a handle to gain entry into cells and cause arthritis. But by introducing blocking antibodies, the team were able to create decoy handles that divert the virus from the true handle and reduce the rate of infection. Compared to a control group, mice that were so treated exhibited between 10- and 100-times less infection in their ankles and calf muscles. With respect to implications for treatment development, Dr. Diamond observed, “Not much is known about what Mxra8 does in the human body, so we need more information before developing a drug that targets Mxra8. But we could more immediately develop a drug that targets the virus and prevent it from attaching to this protein.”
Read a news story about the findings.
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