Deadly viruses focus of $18 million grant

In an effort to learn why some viruses such as influenza, Ebola and West Nile are so lethal, a team of U.S. researchers that includes Washington University School of Medicine in St. Louis plans an $18.3 million comprehensive effort to model how humans respond to these viral pathogens.

The study, funded by the National Institutes of Health (NIH), will be led by Yoshihiro Kawaoka, DVM, PhD, a professor at the University of Wisconsin-Madison School of Veterinary Medicine and an authority on influenza and Ebola viruses.


Kawaoka’s collaborators include West Nile virus expert Michael Diamond, MD, PhD, a Washington University professor of medicine, and researchers from the Pacific Northwest National Laboratories in Richland, Wash.

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 an infection and to make predictions about the causes of disease, which will then be tested in animal models.

Recent discoveries from Diamond’s laboratory include identification of genes that are induced by an immune protein known as interferon. These genes can decrease the vulnerability of cells to infection. Diamond’s research has emphasized the effects of these genes, which are active in the brain.

“The three viruses that the collaborative team will study —West Nile, Ebola, and influenza A — each cause distinct clinical syndromes,” Diamond said. “The ability to compare cellular responses to these highly pathogenic viruses will allow us to define common and unique molecules and mechanisms that prevent infection and severe disease.”

The work on avian influenza and Ebola viruses will be conducted at UW-Madison and Rocky Mountain Laboratories in Hamilton, Mont.

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,” said Kawaoka, “so the host response
is a very important component of the study.”

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 stressed, as no antiviral agents are approved for use against Ebola or West Nile viruses and because there are indications that drugs used to treat influenza virus are losing their effectiveness as the virus 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 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,” said Kawaoka. “It is necessary that we find new agents to protect us from these diseases.”

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.