Transmission dynamics of Avian Influenza A virus

Abstract

Influenza A virus (AIV) has an extremely high rate of mutation. Frequent exchanges of gene segments between different AIV (reassortment) have been responsible for major pandemics in recent human history. The presence of a wild bird reservoir maintains the threat of incursion of AIV into domestic birds, humans and other animals. In this thesis, I addressed unanswered questions of how diverse AIV subtypes (classified according to antigenicity of the two surface proteins, haemagglutinin and neuraminidase) evolve and interact among different bird populations in different parts of the world, using Bayesian phylogenetic methods with large datasets of full genome sequences. Firstly, I explored the reassortment patterns of AIV internal segments among different subtypes by quantifying evolutionary parameters including reassortment rate, evolutionary rate and selective constraint in time-resolved Bayesian tree phylogenies. A major conclusion was that reassortment rate is negatively associated with selective constraint and that infection of wild rather than domestic birds was associated with a higher reassortment rate. Secondly, I described the spatial transmission pattern of AIV in China. Clustering of related viruses in particular geographic areas and economic zones was identified from the viral phylogeographic diffusion networks. The results indicated that Central China and the Pearl River Delta are two main sources of viral out flow; while the East Coast, especially the Yangtze River delta, is the major recipient area. Simultaneously, by applying a general linear model, the predictors that have the strongest impact on viral spatial diffusion were identified, including economic (agricultural) activity, climate, and ecology. Thirdly, I determined the genetic and phylogeographic origin of a recent H7N3 highly pathogenic avian influenza outbreak in Mexico. Location, subtype, avian host species and pathogenicity were modelled as discrete traits and jointly analysed using all eight viral gene segments. The results indicated that the outbreak AIV is a novel reassortant carried by wild waterfowl from different migration flyways in North America during the time period studied. Importantly, I concluded that Mexico, and Central America in general, might be a potential hotspot for AIV reassortment events, a possibility which to date has not attracted widespread attention. Overall, the work carried out in this thesis described the evolutionary dynamics of AIV from which important conclusions regarding its epidemiological impact in both Eurasia and North America can be drawn.