UAF scientist hopes to unravel secrets of rabies virus

RabiesA scientist and professor at the University of Alaska Fairbanks is studying how rabies can alter the brain and affect its host’s behavior to increase the spread of the disease.

Karsten Hueffer, lead author of the study and a professor of veterinary microbiology at UAF, said he hopes the research will help scientists understand the disease and improve treatment.

The study, published in the journal Scientific Reports, discusses how the virus can bind to and inhibit certain receptors in the brain, which in turn affects the host’s behavior.

Hueffer said he came up with the idea over dinner with a colleague.

“I got started on this after chatting with a neurobiologist that works on these receptors, Marvin Schulte, who at the time was working at UAF,” Hueffer said. “During dinner we were wondering if binding of the virus to the receptor could change function of the receptor and alter behavior.”

As it turns out, it could. The binding of the virus with the receptors in the brain affects communication in the brain and induces “frenzied behavior” that increases the chances of spreading the disease.

Hueffer said he started the research because he wanted to know more about why behavior is affected.

“Many infectious agents change behavior in their host, but we do not understand how they do this,” he said. “Our study provides, for the first time, a detailed molecular mechanism for how an infectious agent induces specific behaviors.”

Earlier research on the virus focused on how it binded to receptors in muscles, not in the brain — Hueffer said. This research showed that a molecule called glycoprotein sits on the surface of the rabies virus and can bind to what are called nicotinic acetylcholine receptors in muscles. This research also found a string of amino acids within the glycoprotein that was almost identical to the one found in snake venom that inhibits nicotinic acetylcholine receptors.

Hueffer said he and Schulte made a connection between the two.

“We knew that nicotinic acetylcholine receptors — which bind to the virus in muscles — are also found in the brain, and we presumed that virus could also bind to such receptors,” Hueffer said. “If snake venom has a similar structure to parts of the virus, and inhibits these receptors, we thought maybe the virus could also inhibit these receptors in the brain. Furthermore, we thought that this interaction could influence behavior.”

Hueffer then connected with co-author and former UAF researcher Michael Harris to work on experiments to test whether the rabies virus glycoprotein does, in fact, alter behavior in animals.

“The viruses collect in the spaces between brain cells during the early stages of infection,” Harris said. “These spaces are where brain cells communicate. We thought that if viruses could bind to receptors in these spaces and change how brain cells normally communicate, the virus could change behavior of the infected animal.”

In one experiment, Hueffer and his team injected some of the rabies virus glycoprotein into the brains of mice. Hueffer said the behavioral changes were almost immediate.

“When we injected this small piece of the virus glycoprotein into the brain of mice, the mice started running around much more than mice that got a control injection,” Hueffer said. “Such a behavior can be seen in rabies-infected animals as well.”

Hueffer said drawing conclusions is a challenge because the behavior is easier to study than the virus itself. Other than a slight inflammation, rabies does not often physically affect the brain, making it difficult to detect without sampling brain cells.

Hueffer said this research is the first of its kind to show the connection between brain receptors, behavioral changes and the spread of the disease. Although the research has come a long way, Hueffer said he’s looking forward to the next step.

“Next we want to describe the specific behaviors that this region induces in mice,” Hueffer said, “and also describe more specifically what receptors the virus might inhibit.

“There are many different subtypes in the brain. Figuring out which of these are important could help design drugs more rationally to maybe help treat this disease that is nearly 100 percent fatal.”

Rabies kills 59,000 people annually.

Source: Daily News-Miner