Virologist
Emerging and Infectious Diseases
Southern Research Institute
2000 Ninth Avenue South
Birmingham, AL 35205
205-581-2717
William E. Severson, PhD is a Research Virologist for the Emerging Infectious Disease Research Program at Southern Research. His current research interests focus on High-Throughput approaches to identify new molecular probes that inhibit RNA pathogenic viruses such as avian influenza strain H5N1 viruses. He has 10 years of BSL 2 and BSL 3 experience studying emerging pathogenic viruses. Dr. Severson received his Ph.D. in Molecular Biology from New Mexico State University where he characterized the biochemistry of the Hantavirus nucleocapsid (N) protein-RNA interactions and examined the role the N protein plays in regulating viral transcription and replication. He is the recipient of a Molecular Biology Program Research Fellowship and Award from NMSU. He received a M.S. in Veterinary Molecular Biology and B.S. in Microbiology from Montana State University. His Master's degree involved the development of a nucleic acid-based diagnostic assay for trichomoniasis. This technology served as the foundation to launch a small biotech company (Agricultural Bioengineering Inc.). He has been an invited speaker at the International Congress of Virology and the 5th International Conference for Hantaviruses, HFRS and HPS.
Dr. Severson's research efforts focus on the discovery of novel inhibitors for emerging RNA viruses with an emphasis on chemical probes that modulate host cellular factors. Emerging pathogens are among the most important viruses for human populations since the majority have no vaccines or antivirals, which contributes to their lethality and potential for bioterrorism. These viruses include human pathogens such as influenza viruses (HPAI), coronaviruses (SARS-CoV), West Nile and hantaviruses (Sin Nombre virus). Hantaviruses, classified as select agents, can cause two diseases when transmitted to humans, namely, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). They can potentially be used as a biological weapon due to their high mortality rate and infectivity by the aerosol route. There are no vaccines, immunotherapy or antiviral drugs for HPS. Recently, we have shown that ribavirin, a nonimmunosuppressive nucleoside analogue, causes error prone Hantaan virus (HTNV) replication resulting in "error catastrophe" in vitro.
While exploitation of lethal mutagenesis may yield new promising drugs, it is clear that new approaches are needed for hantaviruses and other virus that cause acute infections. One area that has not been actively pursued for treatment of these viruses is targeting of the host immune system to modulate the clinical course of the disease. For examples, most immune cells secret a powerful multifamily of inducible cytokines such as interferons (IFNs) among the global cellular proteins activated in response to hantavirus infection. IFN, in turn, triggers the transcriptional activation of a cascade of cellular genes in the JAK-STAT pathway. Consequently, Dr. Severson has a key interest in identifying and characterizing new molecular targets for antiviral development with an emphasis on defining novel host targets.
Dr. Severson's research utilizes the BSL-3 facilities for cell culture, animal studies, and immunological approaches to determine how the host-immune response proceeds upon suppression of specific interferon-stimulated gene products (ISGs) in the presence of virus infection, and how this information can be used to screen viral inhibitors against these pathogenic viruses to discover chemotherapeutic agents that target host cellular factors.