Researchers link West Nile symptoms, causes
Eight years in the making, a team of USU researchers has discovered an important aspect of West Nile Virus that may pave the way for new treatments and eventually a cure.
The key they found lies in the many varied symptoms of West Nile Virus, said Dr. John Morrey, director of the Institute for Antiviral Research.
“It’s true that people who have severe, near-fatal disease, those that have respiratory insufficiency, they have a very poor clinical outcome.” said Morrey. “The thing that really determines that is respiratory failure. It seems to correlate with what happens in humans.”
“People who have blurred cognition, memory problems, paralysis, eye problems or other serious symptoms don’t have necessarily a poor prognosis,” he said. “It was because the symptoms are so varied that it is difficult to see what fatal cases had in common.”
“It wasn’t just a bright idea that came along. We had to do experiments along the way to formulate the hypothesis,” Morrey said.
All the little discoveries along the way, some which seemed tiny or insignificant, helped them to form their hypothesis. Little by little, the results of their experiments led them down a path of discovery until they theorized it could be respiratory failure, he said.
“We had the design and the experiments that would answer the question,” he said. “We are studying the cause and effect of West Nile virus induced infection or lesions on the central nervous system,” said Venkatraman Siddharthan, a senior researcher on the project.
Later, they started zeroing in on where the West Nile Viral lesions are and determining what physiological systems are being damaged. The lesions form on the neural pathways that control respiratory action, said Neil Motter, a senior research technician working on the project.
“Basically we can determine if the West Nile Virus infection has reduced the nerve’s velocity and also determine how much damage the nerve has gone through by estimating how well the nerve controls the muscle, where it enters the muscle,” Motter said.
Respiratory centers in the central nervous system in particular have lesions on infected cells, so the team measured the respiration of the infected animals using a technique called Plethysmography, which measures all the respiratory parameters, said Siddharthan. They observed very early on during the course of the infection that reduced respiratory parameters strongly correlate with infection and lesions on the respiratory centers.
What they’ve found with West Nile Virus may also apply to many other types of viral encephalitis. Encephalitis is irritation and inflammation of the brain. The team is finding the same pattern exists for other viruses, Morrey said.
“Ultimately it will be a sort of paradigm shift in how researchers think about these brain diseases,” he said.
“It will open the way to start research investigating that part of the brain that causes this respiratory failure,” Morrey said. “It could affect how physicians manage the disease clinically or how discoveries for new drugs might be made. The techniques that we have been able to do as a team are techniques that are used by neuroscientists to study brain diseases.”
“We’ve been able to apply those to viral diseases, and it has helped us find the answers to this question,” Morrey said. “This is the first time anything like this has really been done on viral encephalitis.”
They conduct experiments by utilizing plethysmography, electromyography, a technique for evaluating and recording electrical activity in muscles and optogenetics, a way of probing neural circuits by combining optical and genetic techniques, Motter said.
“Optogenetics, as far as we know, has never been used in a virus study,” he said. “In this field we are pioneering the technology. We are proving things we could have only dreamed about a few short years ago.”
Currently, USU employs student technicians who learn about the forefront of this research, many of them pre-med students who will be utilizing this knowledge and skills in their future. These new discoveries will also help with funding here at USU, so scientists can move forward their research, Motter said.
“Students who are looking to get into virology, neurosciences and even animal sciences should be very happy and intrigued that USU has such a commitment to this field,” Motter said. “Our research is growing in leaps and bounds and should open new doors for upcoming young scientists in the field.”
Those students who are curious about this research and other similar fields of science are encouraged to explore their interests in depth, Motter said.
“They need to actually talk to people who do the work,” Morrey said. “If you want to be a scientist, go talk to five scientists and ask them the critical questions.”
They need to reach beyond their classes and talk to people who actually do the work for a living, he said.
“We all feel our research is tremendously important to the welfare of humans,” Motter said. “Our research will help direct doctors and researchers find cures and therapies for people who are infected with West Nile Virus.”
The research is ongoing, said Morrey. He said when communities read the publication of these results, they’ll see if other professionals think it’s a big deal.
The team will see how important it is in the future, but for the USU researchers, it’s a big discovery, Morrey said.
“Our results inform us that we may be closer to understanding the mechanisms of infection and death in animal models that is probably linked and can be correlated with human infections,” Siddharthan said. “We are chasing one of the dreaded viruses that cause serious neurological diseases lately in North America.”
–abhendrix@pentaracorp.com