A close-up of Culex pipiens, a mosquito that is one of the most commone carriers of West Nile virus. Credit: Westend61/ Getty Images.
West Nile virus is a mosquito-borne pathogen first isolated in Africa and now spreading worldwide. About 80% of infected people show no symptoms, 20% get fever and mild aches, and fewer than 1% develop potentially deadly meningitis or encephalitis. In 2022, hundreds of severe cases and dozens of deaths were reported in Italy.
An international research team led by Alessandro Borghesi, from San Matteo Research Hospital in Pavia, and Jean-Laurent Casanova, at the Rockefeller University in New York, discovered that 40% of people with West Nile virus meningitis or encephalitis carry an autoimmune defect that impairs their natural defences against the pathogen1. They have autoantibodies directed against their own type I interferons, which are proteins that attack and kill viruses. The researchers also showed that these antibodies block the protective effect of type I interferons in in vitro cells infected with West Nile virus. “We estimated that the presence of these autoantibodies increases the personal risk of developing a neuroinvasive form of West Nile virus disease by up to 500 times”, says Borghesi. Between 0.5 to 2% of people under 65 and up to 7% over 65 carry autoantibodies against type I interferons. Accordingly, the risk of severe disease is higher in older people.
“It might be useful to screen for these autoantibodies people who live in the areas most affected by West Nile, to identify individuals at increased risk and offer them specific protection against mosquitoes,” Borghesi says. It might also be possible to remove selectively the autoantibodies from the blood of patients with severe disease by a treatment known as therapeutic apheresis, that involves removing blood, separating and removing one of its components and then returning it to the patient. But the safety and effectiveness of this procedure still needs to be evaluated in large-scale clinical trials.
The mechanism underlying the other 60% of West Nile virus cases that lead to encephalitis or meningitis is yet to be discovered.
