By Michael Howell
National Institutes of Health (NIH) scientists at Rocky Mountain Lab in Hamilton have filled a research gap by developing a laboratory model to study ticks that transmit flaviviruses, such as Powassan virus. The researchers say the culture model will greatly increase knowledge about how flaviviruses infect ticks and could become a tool to evaluate medical countermeasures against tick-borne viruses. Learning how this flavivirus works in ticks could lead to a better understanding of how other flaviviruses such as West Nile Virus and Zika Virus work in mosquitos.
It’s not surprising that this kind of innovative research method should emerge at RML, according to Dr. Marshall Bloom, Chief of Biology of Vector-Borne Viruses at the Laboratory of Virology at Rocky Mountain Lab.
“This institution was founded on tick research,” said Bloom. “For more than a hundred years our scientists have studied infectious agents carried by various ticks.”
According to Bloom the focus of the research, the Powassan Virus, and the closely related deer tick virus, are the only flaviviruses known to be spread by ticks in North America.
In the last 10 years, about 75 cases of Powassan virus infection have been reported in the U.S., according to the Centers for Disease Control and Prevention. Powassan virus infection can result in fever, headache, vomiting, weakness, confusion, seizures, memory loss, and death. No licensed treatments or vaccines are available for Powassan virus disease. Although it is not a common infection in the United States, Bloom said, reported infections are increasing in the northeastern and upper Midwest in the United States.
“People are beginning to pay attention to the disease in that area,” said Bloom. He said the same tick (Ixodes Scrapularis) that spreads the Powassan virus spreads Lyme Disease.
Bloom said the lead author of the recent study [J Grabowski et al. Flavivirus infection of Ixodes scapularis (black-legged tick) ex vivo organotypic cultures and application for control. mBio DOI: 10.1128/mBio.01255-17 (2017).], Jeff Grabowski, got interested in an aspect of the life-cycle of this virus that few others were interested in, that is, not how it works on the infected host, but how it works in the tick itself. The ticks don’t’ suffer from it, but they do transmit it. How does that work? Or, better yet, how do you even begin to study how that might work?
What Gabrowski and his team came up with was a very novel way of studying the activity of the virus in the tick by examining its growth in some of the tick’s organs. In order to do this they had to dissect these tiny ticks and remove certain critical organs, the saliva gland, the mid-gut (i.e. digestive tract) and the synganglion (i.e. the tick’s brain). It’s not an easy thing to do. Bloom said that the team was lucky to enlist the aid of retired RML scientist Dr. Tom Schwan.
“As most people know,” he said, “Dr. Schwan is still the area’s tick expert. He came out to help us figure out the best way to work with these ticks and do these tick dissections. His assistance in this project was critical.”
The scientists were able to culture the organs in a petri dish and determine that they were viable for a week. In turn, they were able to infect those organs with the virus and watch it spread. They infected the organs with both the Powassan and a related virus, the Langat. By using the Langat virus they were able to follow the infection’s growth. This virus, when it infects a cell, produces a fluorescent green protein that can be photographed and tracked. They found that Powassan virus and the related Langat virus could infect and spread in salivary glands and midgut.
Langat virus is found typically in Southeast Asia and is an ideal model virus for study because it causes only rare, mild infections in people.
“This means that the team can now go on to identify tick proteins that are responsible for enabling the virus to grow and can possibly identify the tick proteins which try to stop the virus from growing,” said Bloom. “Once we have identified these proteins it could lead to the development of what are called ‘counter measures’ against these elements in an effort to modify, eliminate, or control the virus infection in the tick organs and then test it in the whole tick.”
Bloom called it “a beautifully simple model that is easy to understand and easy to explain.”
“It’s my feeling that it will be used by investigators wanting to study infectious diseases in ticks and with other viruses and even bacteria,” said Bloom.
This tick study was supported by funding from the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.