Virginia Tech faculty receives NIH New Innovator Award to research on influenza transmission

Influenza strikes five to 15 percent of the population and is estimated to cost the U.S. economy a hefty $90 million per year. If researchers can improve the understanding of how environmental conditions affect the ability of the influenza virus to survive and infect others while it is airborne, they may be able to help improve prediction and control of its spread.

Linsey Marr, a Virginia Tech civil and environmental engineering faculty member, has studied the flu virus and late last year led a team that made significant headway in determining how the flu virus survived best- in humidity that was less than 50 percent or above 98 percent. This result may help explain why the disease spikes in winter months in temperate regions, where wintertime heating leads to indoor air with low humidity. Her team's work was published in an academically peer-reviewed journal PLoS One.

Today, Marr is receiving a National Institutes of Health (NIH) New Innovator Award valued at $2.28 million over five years, in support of her research on influenza transmission by bioaerosols. According to the NIH, the award is designed specifically to support unusually creative new investigators with highly innovative research ideas at an early stage of their career. Only 41 such grants were announced today, presented to scientists proposing highly innovative approaches to major contemporary challenges in biomedical research, under the High Risk-High Reward program supported by the National Institutes of Health Common Fund.

Key collaborators on Marr's project will be Elankumaran Subbiah, a virologist in the biomedical sciences and pathobiology department of the Virginia-Maryland Regional College of Veterinary Medicine, and Peter Vikesland, an environmental chemist and nanoscientist in the civil and environmental engineering department of Virginia Tech.

Influenza is responsible for an estimated 36,000 deaths, 3.1 million hospitalization days, and 31 million outpatient visits per year in the U.S. for a total economic burden of $90 million, according to researchers from the Centers for Disease Control.

"It is remarkable that we know so much about the infectivity and pathogenicity of influenza viruses and so little about transmission and the inter-host dynamics of the virus in the environment. Many critical questions remain unanswered surrounding the dominant mode of transmission, seasonality, and factors that enable a certain strain to go airborne," Marr said.

Airborne transmission includes droplets and aerosols emitted by sneezing and coughing.

Marr has hypothesized that "pathogen-environment interactions may play a key role in the transmissibility of the virus. Specifically, evaporation-induced changes in the chemical composition of aerosols, such as lowered pH, increased salt and protein concentrations, crystallization, and/or phase separations, affect the structure and/or function of the virus."

With this award, Marr hopes to further understand the reasons why humidity affects the transmission of the influenza virus.

"Major advances in aerosol science have occurred, yet research on the airborne transmission of diseases do not reflect these developments," Marr explained.

Her prior research in this area leads Marr to believe that this new grant will allow her "to introduce pathogen-environment interactions as playing a significant role in the transmission of infectious diseases."

Last year, her research team including her Ph.D. student Wan Yang of Shantou, China, and Subbiah developed an innovative hypothesis that addressed a question that has stymied researchers for decades: how can humidity affect a virus that is encased in an aerosol? They presented in the PLoS One article for the first time the relationship between the influenza A virus viability in human mucus and humidity over a large range of relative humidities, from 17 percent to 100 percent. They found the viability of the virus was highest when the relative humidity was either close to 100 percent or below 50 percent. The results in human mucus may help explain influenza's seasonality in different regions.

"We added flu viruses to droplets of simulated respiratory fluid and to actual human mucus and then measured what fraction survived after exposure to low, medium, and high relative humidities," said Marr.

At low humidity, respiratory droplets evaporate completely and the virus survives well under dry conditions. But at moderate humidity, the droplets evaporate some, but not completely, leaving the virus exposed to higher levels of chemicals in the fluid and compromising the virus' ability to infect cells.

With her new NIH grant, she will lead an interdisciplinary approach, "essential to making a large leap in understanding airborne transmission of infectious disease," Marr said. The research will span the fields of engineering, virology, and chemistry. Their approach will bring modern aerosol, biological, and nanoscience methods to the problem.

"Results of this research have the potential to promote major advances in predicting the pandemic potential of influenza virus strains, forecasting of disease dynamics, and development of infection control strategies," Marr said.

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