New comprehensive effort to model how humans respond to viral pathogens

In an effort to sort out why some viruses such as influenza, Ebola and West Nile are so lethal, a team of U.S. researchers plans a comprehensive effort to model how humans respond to these viral pathogens.

The study will be led by Yoshihiro Kawaoka, a University of Wisconsin-Madison School of Veterinary Medicine professor of pathobiological sciences and an expert on influenza and Ebola viruses. Teams from Washington University in St. Louis and the Pacific Northwest National Laboratory (PNNL) in Richland, Wash., also will play key roles in the new $18.13 million National Institutes of Health-funded study.

The goal of the study will be to provide a detailed molecular understanding of what occurs when these viruses infect their hosts, providing a foundation for the design and development of a new generation of drugs to thwart infection by some of the world's most serious pathogens.

"When an animal is infected with a virus, all kinds of things happen during the course of infection," explains Kawaoka, "so the host response is a very important component of the study."

The study design entails measuring many parameters of infection, including those intrinsic to the virus and to the host, using high-throughput screening, an emerging technology that employs sophisticated instrumentation with sensitive detection systems and advanced data processing methods to make thousands of measurements in a single experiment. The results of the high throughput screening experiments will be used to model what happens during the infection and to make predictions about the causes of disease, which will then be tested in animal models.

The work on avian influenza and Ebola viruses will be conducted at UW-Madison and Rocky Mountain Laboratories in Hamilton, Mont., while studies on West Nile virus will be led by Michael Diamond at Washington University. The high-throughput technology team will be directed by Richard D. Smith of the Pacific Northwest National Laboratory and the computational modeling team will be led by Katrina Waters, also of PNNL.

The results of the new initiative, according to Kawaoka, will underpin the development of new agents to both prevent and treat potentially lethal viral infections. This is extremely important for human health, he notes, as no antiviral agents are approved for use against Ebola or West Nile viruses, and because there are indications that currently available drugs used to treat influenza virus are losing their effectiveness as it evolves to evade drug activity.

The advantage of studying influenza, West Nile and Ebola, notes Kawaoka, is that the viruses all target different cells and organs for infection. A systematic exploration of how the different pathogens affect their hosts may help identify both common and pathogen-specific response circuits, which could be commandeered as chokepoints to snuff out infection.

"By understanding the disease process and understanding the host response, we can identify new targets for drug development," says Kawaoka. "It is necessary that we find new agents to protect us from these diseases."