New project aims to help pin down the process of West Nile virus transmission

Mosquitoes have been transmitting the West Nile virus to humans in the United States for over 25 years, but we still don't know precisely how the virus cycles through these pests and the other animals they bite.

A federally funded project aims to help pin down the process by using mathematical models to analyze how factors like temperature, light pollution, and bird and mosquito abundance affect West Nile virus transmission. The ultimate goal is to advise health departments of the best time of year to kill the bugs.

I'm hopeful that what we will uncover in this grant will help us to better understand what's driving West Nile virus transmission, and seasonal cycles of transmission, so we can determine when and where to direct control interventions to limit transmission and keep people healthy."

Megan Meuti, principal investigator (PI) on the grant and associate professor of entomology at The Ohio State University

The project, based on Ohio data but structured to develop models adaptable to other U.S. regions, is funded by a $3 million grant from the Ecology and Evolution of Infectious Disease program through the National Institute of Allergy and Infectious Diseases.

West Nile virus (WNV) is the most common insect-borne virus in the U.S. Most infected people have minimal or mild flu-like symptoms, but about 1% can become seriously ill – especially those over 60 or people with chronic health problems – if the virus enters the brain.

Previous research gives us a general idea of how and when viral transmission occurs: As days get shorter, female mosquitoes from the Culex genus, known carriers of WNV, prepare for the winter dormancy period called diapause by fattening up on nectar from flowers – though they may take a viral infection they caught from birds with them into their winter downtime. After mosquitoes emerge from diapause in warmer months, more of them may become infected by taking blood meals from infected birds, and then transmit the virus when they feed on people, horses and other mammals.

Among the questions asked by Meuti's team: How does viral transmission re-initiate each spring, and how does the virus's presence persist in the environment during fall and winter?

The dormancy period appears to be delayed – or even prevented – by artificial light at night and heat in urban areas, according to previous studies in Meuti's lab in the College of Food, Agricultural, and Environmental Sciences. That disruption may mean the mosquitoes in cities are biting humans and animals longer into the fall, and also suggests urban and rural transmission patterns may differ.

"We know humans tend to get infected in the late summer and early fall, and other studies have shown that birds are infected before then, but we don't really know where West Nile virus is going in the winter," Meuti said.

The grant team started collecting mosquitoes and birds last fall and will continuously collect specimens for three years. Urban collection sites are located in Franklin and Lucas counties, and rural sites are in Union and Ottawa counties.

Bird trapping focuses on nine species known to be bitten by Culex mosquitoes: American robins, mourning doves, Northern cardinals, house sparrows, common grackles, European starlings, gray catbirds, Swainson's thrushes and red-winged blackbirds. Researchers tag and release captured birds after collecting blood samples that will show their infection status – never infected, active WNV infection, or antibodies indicating they've been infected and recovered.

During the winter, researchers are collecting mosquitoes spending diapause in culverts to see if they're already infected with the virus. Analysis of the blood contents in mosquitoes' bellies will tell researchers what animals they've been biting – birds, horses or humans. Researchers will also sequence the RNA of the virus detected in mosquitoes.

The data and modeling will enable the team to test their hypotheses about how the transmission process plays out in rural and urban settings. In general, researchers predict mosquitoes are more likely to be infected with WNV over the winter in urban areas than in rural areas, suggesting that in rural areas, migratory birds are infecting mosquitoes, or the virus is spilling over from urban settings – or both.

"If RNA sequences are very similar from fall to spring, that would suggest the virus is staying local and, most likely, the way it's staying local would be in the overwintering mosquitoes. But if we see differences in sequences from fall to spring, that would be more suggestive that it is a new WNV strain or a slightly different strain coming from migratory birds," Meuti said.

"Once we have the models in place, we can predict what West Nile virus transmission might look like in a given year. And in partnership with local health departments and mosquito control districts, our ultimate goal is to understand what's driving West Nile virus transmission and use this information to better predict when and where we can direct specific interventions."

Co-PIs on the grant are Laura Pomeroy, assistant professor of environmental health sciences at Ohio State, who is building the mathematical models; Jaqueline Nolting, assistant professor of veterinary preventive medicine at Ohio State, who is analyzing biological samples from captured birds; and Brendan Shirkey, research coordinator for the Winous Point Marsh Conservancy, who is overseeing collection of birds and mosquitoes. Andrew Bowman, professor of veterinary preventive medicine, serves as senior personnel, designing experiments and assisting with data analysis.