Scientists have snapped high-resolution pictures of the chikungunya virus latched onto a protein found on the surface of cells in the joints, an advance that may pave the way for new treatments against the infection.
Most people who become infected with chikungunya virus develop fever and joint pain that last about a week. However, in up to half of patients, the virus can cause severe arthritis that persists for months or years.
There is no treatment to prevent the short-lived infection from persisting into chronic arthritis. Researchers have uncovered information that could help stop the debilitating condition. A team at Washington University in the US snapped images chikungunya virus latched onto a protein found on the surface of cells in the joints.The protein used in the study was taken from mice, but people have the same protein, and the virus interacts with the mouse and human proteins in virtually identical ways.
The structures, published in the journal Cell, shows in atomic-level detail how the virus and cell-surface protein fit together -- data that promises to accelerate efforts to design drugs and vaccines to prevent or treat arthritis caused by chikungunya or related viruses."Chikungunya arthritis comes on very suddenly and can be very painful - people can barely walk around -- and we have nothing specific to treat or prevent it," said Michael S Diamond, a professor at Washington University.
"Now that we have these new structures, we can see how to disrupt the interaction between the virus and the protein it uses to get inside cells in the joints and other musculoskeletal tissues in order to block infections," said Daved Fremont, a professor at Washington University.Chikungunya and its cousins -- Mayaro, Ross River and O'nyong-nyong viruses -- belong to a family of alphaviruses that are spread by mosquitoes and cause joint pain.
In recent years, such viruses have been infecting people and animals in ever larger regions of the globe.To design effective drugs and vaccines, researchers need a detailed picture of the molecular interactions between the virus and the protein.
Images were obtained using a chikungunya virus-like particle -- which has the shape of a virus but cannot cause infections because it carries no genetic material inside -- as well as fully infectious chikungunya virus.The virus-like particles are being evaluated in clinical trials as a potential vaccine for chikungunya.
To visualise how the virus interacts with the cell-surface protein, the researchers first flash-froze the viral particles attached to the protein. The snap freeze was necessary to keep the particles from being destroyed during the experiment.
Then, the researchers shot a beam of electrons through the sample, mapped where the electrons landed on a detector, and used computer programs to reconstruct the electron density patterns and thereby the 3D structure of the viral particles bound to the cell-surface protein.
The high-resolution structure will aid efforts to screen experimental drugs for their ability to block attachment to the protein on cells in the joints, evaluate whether the antibodies elicited by investigational vaccines are likely to prevent infection, and analyse whether mutations in viruses affect their virulence.
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