David Cool (Committee Co-chair), Mariana Morris (Committee Member), Carol Sabourin (Advisor), Carol Sabourin (Committee Co-chair), Courtney Sulentic (Committee Member)
Master of Science (MS)
Influenza viruses are consistently responsible for an average of 20,000 deaths and 114,000 hospitalizations per year. To a great extent, these viruses always stay one step ahead of the available vaccines and people's immunity year after year because they have the ability to either mutate part of their genetic material, or to be transmitted from one species to another. That same genetic variability explains why highly pathogenic influenza viruses emerge that cause great mortality over several countries resulting in pandemics. Highly pathogenic strains of influenza A virus have emerged occasionally in recent history, producing pandemics such as the one in 1918. The Spanish influenza pandemic of 1918-1919 was uniquely severe, causing an estimated 50 million deaths worldwide. Also unique was the age distribution of its victims: the death rate for young, previously healthy adults, who rarely suffer fatal complications from influenza, was exceptionally high. More recently we have seen the emergence of influenza cases and fatalities involving the H5N1 avian influenza strains. Until an outbreak in Hong Kong claimed six human lives in 1997 (A/Hong Kong/156/97 [H5N1]), avian influenza viruses were thought to be incapable of infecting humans directly. However, the initial H5N1 outbreak has revealed that avian influenza viruses could infect humans without prior adaptation and even cause significant morbidity and mortality in the human population. It has been shown that the 1918 viral hemagglutinin sequence is more closely related to avian strains although it is a human HA. This indicates that the 1918 pandemic strain may have also jumped from avian to human with no prior adaptation or reassortment with a human virus.
For these reasons, scientists have been interested in finding out what makes the 1918 virus different from all others, why avian influenza can be so pathogenic, and how to prevent and better treat infections with this virus. For this study the 1918 pandemic influenza was partially reconstructed by placing the 1918 influenza viral hemagglutinin and neuraminidase genes or the 1918 influenza viral hemagglutinin, neuraminidase and non-structural protein genes in the background of the low-pathogenic A/Texas/36/91 virus. The infectivity and pathogenesis of these two partially reconstructed 1918 influenza viruses were compared to each other as well as to the highly-pathogenic avian influenza A/Vietnam/1203/04 H5N1 virus in the BALB/c mouse model. The A/Vietnam/1203/04 influenza virus acted as a "positive" control for high infectivity and pathogenesis.
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
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