Nav: Home

Why chikungunya, other arthritis-causing viruses target joints

May 16, 2018

Chikungunya virus is a growing threat to the United States and other regions of the world as the mosquito that carries the virus expands its reach. Telltale symptoms of chikungunya infection are fever and joint pain that last about a week. But in up to half of patients, the virus can cause a debilitating form of arthritis that persists for months or even years.

Scientists have understood little about how chikungunya and related viruses cause arthritis. Now, researchers at Washington University School of Medicine in St. Louis have identified the molecular handle that chikungunya grabs to get inside cells. The findings, published May 16 in the journal Nature, could lead to ways to prevent or treat disease caused by chikungunya and related viruses.

The handle, or receptor, is located on cells that build cartilage, muscle and bone. Joints are filled with such cells, which helps explain patients' painful symptoms. Further, by creating decoy handles, the researchers showed that they could reduce chikungunya infection and signs of arthritis.

"The name chikungunya comes from the Makonde language of Tanzania, and it means 'to walk bent over.' That's how painful the arthritis can be," said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine at the School of Medicine. "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.

There are no specific treatments or vaccines for chikungunya and related viruses, known as arthritogenic alphaviruses. Doctors simply recommend rest, fluids and over-the-counter pain relievers such as acetaminophen or ibuprofen.

With the aid of a warming planet and modern means of transportation, mosquitoes that carry chikungunya and related viruses are spreading. Once limited to Asia and Africa, chikungunya virus has infected more than a million people in the Caribbean and South America in an outbreak that began in 2013 and continues to this day.

Figuring out how the virus gets inside cells is considered a step toward slowing its spread. Diamond, first author and postdoctoral researcher Rong Zhang, PhD, and colleagues identified the protein on cells that chikungunya virus latches onto.

The protein is called Mxra8, and it is needed for chikungunya to invade both human and mouse cells, the researchers found. Additional experiments showed that not just chikungunya but its arthritis-causing relatives - Mayaro, Ross River, O'nyongnyong and Barmah Forest viruses - require the protein to get into cells.

Since chikungunya uses Mxra8 protein as a handle to open a door into cells, the researchers tested whether preventing the virus from grabbing that handle could reduce infection. They deluged the virus with decoy handles, reasoning that chikungunya would grab the decoy and be locked out of cells. Only the few individual viruses that lucked onto a true handle could infect cells, so the overall infection rate - and signs of arthritis - would fall.

And that's just what they found. A day after infection, the level of virus in the mice's ankles and calf muscles was between tenfold and a hundredfold lower in the animals that had been treated with Mxra8 proteins or blocking antibodies than those that received placebo, and the numbers remained lower over the next two days. In addition, three days after treatment, the mice that had received the protein exhibited much less swelling in their ankles than those that received the placebo.

The results suggest that a compound that blocks the virus from attaching to Mxra8 on the surface of cells could prevent or reduce arthritis.

"Not much is known about what Mxra8 does in the human body, so we need more information before developing a drug that targets Mxra8," said Diamond, who also is a professor of molecular microbiology, and of pathology and immunology. "But we could more immediately develop a drug that targets the virus and prevent it from attaching to this protein."

The researchers are working on mapping the structure of the protein and locating the exact spot to which the virus attaches. Such information could help researchers design a compound to interfere with the virus's ability to hold onto the protein, or to design vaccines to prevent infection.
-end-


Washington University School of Medicine

Related Arthritis Articles:

Eating fish may reduce arthritis symptoms
In a recent study, individuals with rheumatoid arthritis who consumed fish 2 times/week had lower disease activity (swollen/tender joint counts along with other assessments) than those who ate fish never to <1/month.
Coping with arthritis: What you do isn't associated with how much information you want
Arthritis patients were more likely to be high monitors (health detail oriented) than high blunters (health detail avoidant) in a study led by the University of North Carolina Eshelman School of Pharmacy.
Fish get arthritis, too
The very first bony fish on Earth was susceptible to arthritis, according to a USC-led discovery that may fast-track therapeutic research in preventing or easing the nation's most common cause of disability.
Arthritis linked to suicide attempts
One in every 26 men with arthritis have attempted suicide compared to one in 50 men without arthritis.
Osteoarthritis just as severe as rheumatoid arthritis
Rheumatologists more likely to underestimate clinical status of their OA patients than their RA patients
Blood test that could predict arthritis risk
Testing for antibodies that target citrullinated tenascin-C (cTNC) could diagnose RA in around 50 percent of cases, including some cases not identified by current best tests.
New strategy discovered for treating arthritis
Arthritis patients could one day benefit from a novel form of medicine, according to researchers at Queen Mary University of London.
Arthritis may be a major driver of poverty
Developing arthritis increases the risk of falling into poverty, especially for women, new research shows.
No innocent bystander: Cartilage contributes to arthritis
Melbourne researchers have discovered that cartilage plays an active role in the destruction and remodeling of joints seen in rheumatoid arthritis, rather than being an 'innocent bystander' as previously thought.
Blocking one receptor could halt rheumatoid arthritis
Researchers at the University of Illinois at Chicago College of Medicine have shown for the first time how the activation of a receptor provokes the inflammation and bone degradation of rheumatoid arthritis -- and that activation of this one receptor, found on cells in the fluid of arthritic joints, is all that is required.

Related Arthritis Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".