Herbert Newby McCoy Award
2008 McCoy Award Recipient
Richard Kuhn
Professor of Biological Sciences
Pursuing Dengue Virus: A 21st Century Scourge
Richard Kuhn completed his undergraduate studies in biochemistry at the State University of New York at Stony Brook. In 1981 he joined the Department of Microbiology where he did graduate research studying poliovirus replication in the laboratory of Dr. Eckard Wimmer. After receiving his PhD in molecular virology in 1986 he joined the laboratory of Dr. James Strauss at the California Institute of Technology. He was recruited to Purdue University as an assistant professor in the Markey Center for Structural Biology in 1991. He was appointed Head of the Department of Biological Sciences in 2005 and the Director of the Bindley Bioscience Center in 2007. His research at Purdue has focused on the replication and assembly of alphaviruses and flaviviruses. Together with his structural biology colleagues especially Michael Rossmann, he has been involved in many fundamental studies examining the structure and assembly of enveloped viruses, including the first structure of dengue virus. His focus continues to be in virus replication, virion assembly, pathogenesis, and host cell interactions using biochemical, genetic, and structural techniques. Professor Kuhn was elected a Fellow of the American Academy of Microbiology and the American Association for the Advancement of Science (2007), selected as a Purdue University Faculty Scholar (2004–2009) and is a member of the U.S. Panel on Viral Diseases of the US-Japan Cooperative Medical Sciences Program. He serves on the editorial boards of the Journal of Virology, and Virology, and is the author of over 100 publications.
Abstract of Lecture
The flaviviruses are an important group of human pathogens that are found worldwide. They include members such as hepatitis C virus, yellow fever virus, West Nile virus, and dengue virus. Dengue has become the most important of the insect-transmitted human viruses, with 2 billion people at risk, and 50 million infections each year. The laboratory has focused on investigating the life cycle of the virus by the integration of structural, biochemical, and molecular genetic approaches. These analyses allow powerful ‘structure-function' studies in which dissecting the atomic composition and layout of the virus and its components permits one to interpret how they work together to allow the virus to replicate. This talk will present an overview of the dengue virus life cycle and how we are closer to understanding this important human pathogen and developing new intervention strategies.
Research Challenges
Professor Kuhn's major expertise is in the field of molecular virology. The application of his expertise in collaboration with laboratories in structural biology, using x-ray crystallography, NMR, and electron microscopy to analyze viruses and macromolecular structures, has created at Purdue University one of the very best, most productive, and best-known virus structure-function laboratories in the world. The collaborative mode of experimental research that describes the interactions of these individuals is characteristic of many of the best modern-day laboratories in the biological sciences.
The Kuhn laboratory is studying the molecular mechanisms involved in virus gene expression and the nature of virus-host interactions. An understanding of these two related areas is essential for a comprehensive model of virus pathogenesis and for a description of the molecular evolution of viruses. We have focused our attention on several groups of RNA-containing viruses that are important human pathogens. Many of these viruses are emerging into new regions of the world. Several specific areas of virus replication are under study: (1) the assembly of the virus particle; (2) molecular analyses of the structural proteins and their role in pathogenesis; (3) structure—function studies of replication proteins; and (4) the design of novel intervention strategies against enveloped viruses.
The laboratory is examining the assembly pathways for several enveloped animal viruses that are important human pathogens. The viruses being studied include Sindbis and Ross River, which are classified as alphaviruses, and hepatitis C, West Nile, dengue, and yellow fever, which are grouped into the flavivirus family. Our approach is to use biochemical, molecular genetic, and structural techniques to gain insight into the molecular requirements for particle formation. During the past several years, the laboratory has made significant progress in understanding alphavirus and flavivirus virion structure and assembly.
The Kuhn laboratory has also initiated an extensive structure-function analysis of the proteins found in the alphavirus and flavivirus groups. Our goal is to solve the atomic structure of all replication and virion proteins and to use that information to guide molecular genetic studies to understand how the proteins function and how that relates to pathogenesis. To this goal, the laboratory has established a variety of in vivo and in vitro systems for studying various aspects of virus replication. We have also established ‘replicon' systems that allow us to study virus-host interactions without the complication of virus particles and repeated cycles of virus infection. These systems are also valuable for screening compounds for antiviral activity.
In collaboration with the Bindley Bioscience Center, the laboratory is exploring a global view of the effect of flavivirus replication on host gene expression. For these studies, data-intensive techniques are employed that include microarrays, proteomics and lipidomics analyses of flavivirus infected cells. This macroscale approach will be followed by a detailed analysis of virushost protein interactions that play a direct role in virulence and disease. The ultimate goal is to achieve an understanding of the relationship between the virus and its human host so that viral disease can be mitigated. Professor Richard Kuhn's research is focused on the molecular mechanisms underlying virus biology—how viral genes are expressed, how viruses are assembled, and the molecular bases for virus-host interactions. Viruses come in many forms: some are enveloped in a lipid-protein membrane, and some are not enveloped; some are spherical, and others include long projections; some contain RNA (plus-stranded or minus-stranded), and others contain DNA. Richard specializes in two families of plus-strand spherical enveloped viruses, the togaviruses and flaviviruses. Richard's lab has worked on several enveloped animal viruses that are important human pathogens, including Sindbis, Ross River, hepatitis C, yellow fever, Dengue, and West Nile.
