Wash U study pinpoints how arthritis-causing virus invades cells
Washington University researchers are one step closer to understanding how a common virus transmitted by mosquitoes causes chronic arthritis.
Like other mosquito-borne diseases, patients with chikungunya virus usually develop a fever and muscle aches. There is no known treatment for the virus, but it often clears up on its own within several weeks. For some patients, however, chikungunya causes severe arthritis that can last for months or even years.
Wash U researchers have now identified a protein on the outside of joint and muscle cells that allows the virus to get inside, causing joint pain.
“Chikungunya means literally ‘that which bends up’ in the Makonde language of Tanzania,” said Michael Diamond, a professor in Washington University's Division of Infectious Diseases. “The arthritis can be very bad, to the point where people are unable to bend their joints and straighten them because the swelling is so painful.”
According to the Centers for Disease Control, chikungunya outbreaks historically have occurred in Africa, Asia and parts of Europe. The virus first appeared in the Caribbean in 2013, sparking concern over the possibility of outbreaks in the southeastern United States.
“For whatever reason, [chikungunya] has not taken a foothold to cause local cases in the United States,” said Diamond. “However, it’s anticipated that at some time, it probably will.”
Unlike bacteria, Diamond said, viruses like chikungunya need to enter a host cell in order to replicate. To get inside the cell, the virus attaches to specific proteins on the outside of the host cell, which act like biological doorknobs.
Using a relatively new technique known as CRISPR-Cas9 gene editing, Diamond and his colleagues at Wash U were able to identify the protein receptor chikungunya virus uses to invade human cells. That receptor, Mxra8, is found on cells that build muscle, cartilage and bone.
When they blocked the protein with a specific antibody in mice, they saw reduced viral infection and less joint swelling.
“This was the tie between identifying the protein as being important to get in the cell and being related to the clinical disease,” Diamond said.
Chikungunya is closely related to other arthritis-causing viruses, including Mayaro, Ross River and O'nyong-nyong viruses. Through a series of experiments, the team determined that the protein acts as an entry point into human cells for these viruses as well.
They're now working to understand how exactly the virus attaches to host cells. This information could prove instrumental in developing a drug that blocks the virus from entering and infecting human cells.
The study appears in the May 16 issue of the journal Nature.
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