West Nile Virus Sparks Synaptic Inflammation Leading to Memory Loss

    Scientists at the University of Colorado Anschutz Medical Campus say they have discovered how the most severe forms of West Nile virus (WNV) cause memory loss and mood disorders, opening the door to potential new treatments for the mosquito-borne illness. Their study (“A Complement–Microglial Axis Drives Synapse Loss During Virus-Induced Memory Impairment”), published in Nature, reports that 50% of patients who survive the most damaging kind of WNV infection often go on to develop memory loss, learning difficulties, a lack of concentration, and irritability.

    Exactly why this happens has been a mystery until now. The virus doesn’t kill off neurons but instead sparks inflammation that prunes synapses, according to the researchers.

    “What we found in mice, and later confirmed in humans, is that it’s not the death of cells that causes memory loss, it’s the loss of nerve cell connections,” said study co-author Kenneth Tyler, M.D., chairman of the department of neurology at the University of Colorado School of Medicine. “The viral infection activates microglial cells and complement pathways which are helping to fight the infection but in turn end up destroying synapses.”

    The researchers noted that mice infected with WNV had a difficult time negotiating their way out of a maze that healthy mice figured out much faster. They later discovered that the infected mice suffered significant damage to their synapses. The scientists examined brain tissue from humans who had died from WNV infection and found the same phenomenon.

    Dr. Tyler said WNV is the leading cause of acute viral encephalitis in the U.S. though still relatively rare. Only about one in 100 people infected with the disease develop the most severe form, he said. WNV appeared in the U.S. during the late 1990s and has remained a persistent threat. Last year, California had 730 cases, Texas 252 cases, and Colorado 101 cases. In Colorado, that number included 57 neuroinvasive cases, the most serious kind, and two deaths.

    “This discovery opens up the opportunity to test therapies and medications on mice as a precursor to humans,” pointed out Dr. Tyler. “We already have some drugs that might be good candidates for treating this condition.”

    The best way to avoid WNV is to wear long sleeves, use mosquito repellent, and steer clear of standing water. The mosquito that carries the virus is most active at dusk and dawn.