Bird flu leaves tracks in brain

Virus might create vulnerability to neurological disorders, research in mice suggests

After surviving a bout of virulent bird flu, mice’s brains show short-term reductions of a key brain chemical and long-lasting signs of infection, a new study finds. The research suggests this type of flu might leave people more vulnerable to brain disorders such as Parkinson’s disease.
While most people think of influenza as a disorder of the body, certain kinds of flu also infect the brain. Recent studies have found that the bird flu virus known as H5N1, which kills about half the people it infects, can set up shop in the brain. But exactly what happens next has been a mystery.
In the new study, scientists at St. Jude Children’s Research Hospital in Memphis, Tenn., examined the brains of mice that had survived an initial H5N1 infection. As in people, the virus kills about half of mice affected.
“The first goal with H5N1 was to characterize the neurological effects,” says study coauthor Richard Smeyne.
After being infected with H5N1 isolated from a Vietnamese boy who died from the flu, some mice initially got very sick, but then seemed to recover completely after about 21 days. Yet the story wasn’t so simple in the brain, the team reports in the Feb. 1 Journal of Neuroscience.
Nerve cells that make one of the brain’s key messengers — the neurotransmitter dopamine, which helps regulate movement — shut down production about 10 days after infection. These nerve cells, which are the same cells that degenerate in people with Parkinson’s disease, “basically take a time out,” Smeyne says. “All efforts are to survive.”
By day 60, the dopamine starts to reappear, and levels are back to normal 90 days later. Signs of inflammation in the brain remain, though.
Just three days into the infection, the brains of these mice showed evidence of a strong inflammatory response, and this response appeared to linger over time. Proteins that accompany inflammation, and cells that patrol the brain looking for threats, were still present and on duty in parts of the brain 90 days after the initial infection. Scientists don’t know whether the response ever goes away. “My guess is that it’s permanent,” Smeyne says.
He notes that it’s unlikely that an influenza infection could cause neurological diseases such as Parkinson’s, but an infection might be a contributing factor, perhaps even precipitating the disease in someone already at risk.
The results are intriguing because they offer a way to understand H5N1’s consequences in the brain, says neuroimmunologist Stephanie Bissel of the University of Pittsburgh School of Medicine. Future experiments on such survivor mice could reveal whether the mice show behavioral signs of neurological impairment, she says.
The research team has evidence that H5N1 breaks into the brain by traveling along the vagus nerve from nerve cells in the gut. The virus might also enter the brain from the nose by crawling along the olfactory nerve, Smeyne says.