Immune system’s response to infection is responsible for neurological damage — not the infection itself

In the aftermath of the Zika virus epidemic and the COVID-19 pandemic, there has been a belief in the scientific community that acute viral infections are directly responsible for neurological damage. However, researchers from McMaster University have now discovered that it might be something else that’s behind it.

“We were interested in trying to understand why so many viral infections are associated with neurological diseases,” said Elizabath Balint, a PhD student at McMaster. “Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage.”

The research, published in Nature Communications on Monday and led by Balint and Ali Ashkar, a professor with McMaster’s department of medicine, focused on the Zika virus. During their testing, they found T cells that were specific for Zika and designed to eliminate infected cells, which they expected. But that wasn’t all they found.

“We identified cells that weren’t functioning like a normal T cell and were killing lots of cells that weren’t infected with Zika,” Balint said. These are called NKG2D+CD8+ T cells and their overly-aggressive response can cause the neurological damage suffered from infections like Zika and COVID-19.

Their response is the result of the body producing large amounts of inflammatory proteins called cytokines. In moderation, they help coordinate the body’s response in battling infection or injury by telling immune cells where to go and what to do when they arrive. But if they’re overproduced, the results can be devastating.

“If our body’s immune cells overreact and over produce inflammatory cytokines, this condition will lead to non-specific activation of our immune cells which in turn leads to collateral damage. This can have severe consequences if it happens in the brain,” Ashkar said.

The McMaster team’s discovery sets a new bar for fellow researchers and scientists to find treatments for neurological diseases sparked by acute viral infections. Ashkar said Balint has already experimented with an antibody that holds promise, one that completely blocks and treats devastating neurotoxicity in animals, and is now in clinical trials for different uses in humans.

Balint hopes to continue her work and find an effective treatment for humans.

“There are a few different other viruses we’re interested in studying, which will aid us in creating the best treatment options,” Balint says.