Genetic and evolutionary dynamics of avian influenza A virus in wild birds

Abstract

Influenza A virus (IAV) is the prototype of the family Orthomyxoviridae, a group of segmented, negative-sense, single-stranded RNA viruses. The virus circulates in wild bird species but does not usually cause severe disease in these hosts. However, highly pathogenic forms exist and have caused numerous deaths in wild and farmed birds. The eastern coast of Canada represents an interesting location for the study of IAVs in their natural reservoir as it has a large number of bird breeding colonies and migratory bird connections with the mainland of North America and Eurasia. Previous research on IAV ecology and transmission has shown that migratory birds in this region move the virus around the globe and contribute an important facet to IAV dynamics. My thesis focuses on the study of the virus genetics and evolutionary dynamics in different wild bird species. By applying high-throughput next-generation sequencing technologies, I characterized complete IAV genomes from different wild bird species from Newfoundland and Labrador and conducted in-depth analyses of the virus genomic structure. My study revealed that the structure of the virus genome is conserved among similar avian hosts. I also demonstrated though experimental mutation studies that a change of host can causes major changes in the viral genome. I also explored evolutionary patterns in the viral genomic non-coding regions (NCRs), and found that variation in the NCR sequences is correlated with the original host species and geographic origin. Finally, I analyzed IAVs from Laridae family hosts (gulls and terns) and demonstrated that these hosts are important for the transmission of IAVs around the globe and to other hosts and participate in the generation of pandemic viruses. Overall, my results contribute to give a better understanding on the evolution and geographic patterns of influenza A viruses in their natural hosts.