RNA viruses with zoonotic potential represent a public health threat throughout the world. High mutation rates, short generation times and large population sizes are three factors responsible for their high genetic variability and enormous adaptive capacity to new environmental conditions. Understanding the genetic properties and the evolutionary dynamics of RNA viruses with zoonotic potential is crucial to prevent, control, treat and lessen the damage to animal and human health.
This thesis investigates the most essential aspects related to the evolution and epidemiology of two widespread zoonotic diseases caused by two RNA viruses: Avian Influenza and rabies. Through the application of bioinformatics tools, I analysed a large amount of sequence data, generated using both first and second generation sequencing technology, from viruses collected during four distinct epidemics: a fox-rabies virus epidemic occurred in north-eastern Italy between 2008 and 2011, highly pathogenic H5N1 avian influenza outbreaks reported in Egypt between 2006 and 2010, and two avian influenza epidemics caused by two distinct subtypes that took place in northern Italy from 1999 to 2001 and 2002 to 2004.
Through phylogenetic and Bayesian phylogeographic analyses of viral sequences sampled over multiple discrete spatio-temporal scales, the studies in this thesis reveal the co-circulation of multiple viral lineages, explore the viral gene flows and investigate the evolutionary dynamics of viruses under different selection pressures. In addition, to better understand the pattern of transmission of viral subpopulations from host to host, the intra-host variability and the evolution of viral pathogenicity, I employed an ultra-deep sequencing approach to assess the diversity of viral populations.
The data generated in this thesis provide important insights into the a) impact and efficacy of surveillance strategies and control measures implemented during an outbreak, b) differences in the evolutionary dynamics and spatial spread between distinct genetic groups, c) emergence of amino acid mutations that may increase viral fitness, d) inter-host transmission of viral variants and e) gain of virulence determinants.
Finally, this thesis shows the great opportunity offered by next generation sequencing technology for dramatic advancement in our understanding of the complicated evolutionary dynamics of these pathogen
