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.