Lineage Establishment and Replacement of H6 Subtype Influenza Viruses in Ducks in Southern China

This dissertation, "Lineage Establishment and Replacement of H6 Subtype Influenza Viruses in Ducks in Southern China" by Kai, Huang, 黄楷, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Waterfowl are the primary hosts or natural reservoirs of influenza A viruses. Modern agricultural practices have led to two thirds of the world's domestic ducks being intensively farmed in China and created a reservoir host resource of unprecedented size for the influenza virus. The viruses of poultry and mammals were originally derived from waterfowl viruses and over the last two decades several lineages of influenza viruses have emerged and become established in poultry in this region. Due to sporadic human infections, these viruses pose a persistent pandemic threat to the world. H6 is one of the most frequently detected subtypes in ducks, based on long-term influenza surveillance in southern China. Consequently, it was selected to investigate changes in the current influenza ecosystem of this region by exploring how H6 viruses evolve in their natural reservoir host and interact with the influenza virus gene pool. A total of 461 H6 duck viruses, isolated from seven provinces in southern China from 2000 to 2007, were genetically and phylogenetically characterized. Three distinct groups of H6 viruses were identified (Groups I, II and the gene pool). The Group I and II viruses were mainly predominant in the coastal regions (Guangdong and Fujian provinces), while the gene pool H6 viruses were mainly found in inland regions. Group I and II viruses formed two distinct phylogenetic lineages while the gene pool viruses were interspersed among the Eurasian gene pool viruses. Genotyping of the H6 viruses tested showed that Group I and II viruses had a relatively fixed internal gene cassette. Features characteristic of viruses established in aberrant hosts, such as deletions in the stalk region of the NA protein and C-terminal truncations of the NS1 protein were found in these viruses. Both the Group I and II H6 viruses appear to have become established in this natural reservoir host. Group I viruses were present when sampling commenced, while Group II virus emerged later and became common when Group I viruses disappeared in 2005. Subsequently, Group II viruses have expanded their distribution to other provinces and neighboring countries. A change in the predominant NA subtype from N2 to N6 was observed in the Group II viruses, possibly related to changes in HA-NA balance. An apparent change in the replication site from intestine to trachea appeared to be occurring in the Group II viruses. This thesis has shown that the domestic duck can have dual roles in the influenza ecosystem. It may act as a reservoir host or as a host facilitating the establishment of virus lineages. This could allow the domestic duck to act as an intermediate host to facilitate the transmission of gene pool viruses, via establishment, to terrestrial poultry or mammalian hosts. Whether the established H6 viruses detected here could become more easily introduced to other species requires further investigation. DOI: 10.5353/th_b4852163 Subjects: Avian influenza A virus - China