Key muscle protein may unlock the mystery of chronic mosquito-borne viral illness

Underlying evolutionary dynamics could play a key role in the replication and progress of the chikungunya virus, a mosquito-borne viral disease. New research from Ph.D. student Wern Hann Ng, Dr. Xiang Liu and Professor Suresh Mahalingam from Griffith University's Menzies Health Institute Queensland, shows the mechanism by which the chikungunya virus leverages a host protein.

The paper, "FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design," has been published in Nature Communications.

Wern Hann Ng said the chikungunya virus infection causes clinical symptoms such as joint and muscle pain, as well as joint swelling. "The mortality rate is low, however, the virus can cause acute and chronic debilitating musculoskeletal disease, which is why it's important to understand the mechanics of the virus," he said.

"Our research showed the host protein, four-and-a-half-LIM protein (FHL1), a crucial protein in muscle physiology, is important for virus replication, leading to disease.

"Of the four closely-related alphaviruses tested, FHL1 regulates replication and disease only in the chikungunya and o'nyong-nyong viruses. This is not the case for the Ross River and Mayaro viruses, potentially indicating an underlying evolutionary dynamic."

Dr. Liu said the team discovered the non-structural protein (nsP3) of both the chikungunya and o'nyong 'nyong viruses binds to FHL1.

"In contrast, such binding does not occur with Ross River and Mayaro viruses," he said. "This is a classic example of how the virus uses host proteins for its survival.

"We may have identified a central mechanism underlying chronic chikungunya disease and targeting FHL1 could be a promising strategy to mitigate the severity of chronic illness."

Most cases of chikungunya are predominantly found in the Pacific region, Africa, Asia and the Americas, but in recent years, local transmission has been reported in Europe.

Professor Mahalingam said chikungunya virus has an expanding global distribution and presents a clear danger of major outbreaks in the future.

"With climate change, outbreaks are expected to become larger and more frequent due to increased distribution of mosquito populations," he said. "Cutting-edge discoveries such as this will help unravel mechanisms of disease that will inform new translational opportunities."