NIH Scientists Identify Possible Mechanism of Virus-Induced Brain Damage
La Crosse virus uses immune system proteins to induce death of nerve cells
The immune system protein SARM1 (red) extends to the string-like fibers of nerve cells, or neurons, in the brains of mice infected with La Crosse virus. Scientists are studying whether SARM1 uses these fibers, also called axons, to kill other neurons. Credit: NIAID
Background
La Crosse virus (LACV) is known to infect neurons and cause brain damage. Discovered in 1963 in Wisconsin, LACV is a common cause of encephalitis, or brain swelling, in children under age 16. There are about 80 cases of severe LACV disease in the United States each year. In addition, less severe cases of LACV are significantly under-reported or under-diagnosed, according to the Centers for Disease Control and Prevention. There is no specific treatment for La Crosse virus. Mosquitoes spread the virus from small rodents, such as chipmunks and squirrels, to humans. LACV is fatal in less than 2 percent of cases, but it also can result in seizures, coma, paralysis, and other neurological disorders.Results of Study
By studying LACV infection in cell cultures of neurons and in mice, scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) determined that LACV uses a protein called MAVS to activate early immune responses. They then showed how MAVS induces another immune system protein, SARM1, to kill neurons (SARM1 binds to and damages mitochondria—the cells’ energy source). In study models where scientists removed SARM1, significantly fewer neurons died despite similar LACV infection.Normally, MAVS stimulates the immune system to produce type 1 interferon, which limits infecting virus from replicating and spreading. In neurons, however, MAVS activation results in the death of the neuron by inducing the production of SARM1.
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