Investigators and Program Directors
David E. Wentworth
Research Scientist, Wadsworth Center, Viral Disease
Assistant Professor, School of Public Health, Biomedical Sciences
Ph.D., University of Wisconsin-Madison
Postdoctoral training, University of Colorado Health Sciences
Center
E-mail: dwentwor@wadsworth.org
Research Interests
INFLUENZA AND CORONAVIRUSES: EMERGING DISEASE THREATS
The long-term goal of our research is to understand the molecular mechanisms of interspecies transmission and pathogenesis of viruses. My laboratory studies the molecular biology of influenza and coronaviruses in order to understand the adaptation of a virus to a new host and to identify molecular determinants critical to pathogenesis of viruses. Influenza A viruses and coronaviruses cause a wide range of disease in humans and many other animal species. Furthermore, both viruses cross species barriers in the natural setting and this may lead to increased disease in the new host.
Influenza Virus:
There are three types of influenza viruses, Type A, B, and C. All three types infect humans; however, type A is of the most concern and it infects many other animal species. The influenza A genome is made up of eight different strands of negative sense RNA that code for ten-eleven proteins. Antigenic drift variants of classical human influenza A viruses (e.g., H3N2 and H1N1) re-emerge annually and infect ~500 million people worldwide during a moderate year. Periodically new antigenically distinct viruses emerge and these antigenic shift variants cause pandemics that rapidly kill millions of people. Interspecies transmission is critical to the evolution and pathogenesis of antigenic shift viruses with pandemic potential. Emergence of novel H5N1 and H7N7 subtypes of influenza A in people of Asia and the Netherlands illustrates that the potential for the emergence of a new pandemic strain of human influenza is very high. Our laboratory uses the reverse genetics procedure developed in the lab of Dr. Yoshihiro Kawaoka to genetically engineer influenza A viruses in order to study mutations associated with viral adaptation to new host species, and cis-acting RNA and/or protein determinants important in the highly pathogenic nature of avian H5 influenza viruses. In addition, we are developing high throughput techniques for influenza A detection and genetic evaluation to determine the pandemic potential of new isolates.
Coronavirus:
Coronaviruses are diverse enveloped, positive-stranded RNA (~30kb) viruses that infect humans, other mammals and avian species. Large glycoproteins called "spikes" protrude from the virus surface and are responsible for binding to the host cell receptor. We study the interaction of the coronavirus spike with the host cell receptor because this is a major determinant in species specificity and pathogenesis. A recent outbreak of Severe Acute Respiratory Syndrome lead to the discovery that a novel coronavirus called SARS-CoV emerged in Guangdong Province, People's Republic of China in November 2002. SARS-CoV spread to 30 other countries and caused 8,098 reported cases, which resulted in 774 fatalities. Our current coronavirus research focuses on developing transgenic mice, and other small animal models to study pathogenesis, antivirals, and vaccines. We are also creating and using reverse genetic approaches to genetically engineer coronaviruses in order to investigate viral adaptation after emergence in a new host, spike-receptor interactions, and cis-acting RNA elements important in replication and/or pathogenesis.
Contact Information
E-mail: dwentwor@wadsworth.org.