ADAPTIVE EVOLUTION OF ZOONOTIC AND EPIZOOTIC INFLUENZA A VIRUSES

Abstract

Influenza A viruses (IAV) are important respiratory pathogens that cause significant morbidity and mortality in different avian and mammalian species, including humans. A pandemic or panzootic occurs when a new IAV antigenic variant emerges upon transmission and adaptation to new hosts via reassortment of gene segments. Understanding the drivers of interspecies transmission and elucidating the mechanisms of emergence in new hosts are crucial for global preparedness and response to future outbreaks. In this thesis I examine three major interspecies transmission events that caused pandemics or outbreaks: human H2N2 in 1957, human H7N9 in 2013, and a swine H1N1 in 1979. First, I investigate the emergence of the 1957 H2N2 pandemic as a result of a zoonotic transmission of novel avian IAV segments into human circulation, and discuss the adaptive changes therein. Second, I examine the zoonotic transmission of H7N9 IAV from poultry to humans that are still circulating to date, and the results identified three amino acid mutations in the matrix protein segment that may be associated with increased severity in humans. Finally, I elucidate the emergence of the European avian-like swine H1N1 viruses as a result of an epizootic transmission from avian IAV to swine. The findings reported in this thesis will be useful for contributing to global IAV surveillance efforts by identifying and understanding potential adaptive genetic markers that underlie host jumps.