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This dissertation, Molecular Epidemiology of Avian Influenza Viruses From Southeastern China by 錢寶生, Po-san, Mario, Chin, 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: Abstract of thesis entitled Molecular Epidemiology of Avian Influenza Viruses from Southeastern China by Chin Po San, Mario for the degree of Doctor of Philosophy at The University of Hong Kong in January 2003 The H5N1 'bird flu' incident that claimed six lives in Hong Kong in 1997 was generally considered to have been an incipient pandemic. Chicken in the live poultry markets were the principal source of the highly pathogenic H5N1 (H5N1/97) viruses raising the possibility that terrestrial poultry could become a source of pandemic influenza viruses. To explore this hypothesis, influenza virus surveillance was conducted in Hong Kong on wild aquatic birds and on terrestrial poultry from southeastern China. Influenza virus surveillance of wild aquatic birds at the Mai Po Nature Reserve from March 1999 to February 2001 yielded a lone H3N8 virus from 1077 faecal samples. Thus, these birds are not a major reservoir of influenza viruses and are unlikely to be responsible for the viruses isolated from domestic poultry in Hong Kong and immediate southeastern China. By contrast, 4286 faecal samples from eight types of terrestrial poultry in live-poultry retail markets from April 1999 to May 2000 yielded 209 H9N2 viruses from seven types predominantly quail and six H6N1 viruses from quail, chukar and pheasant. These H9N2 viruses have six H5N1/97-like genes paving the way for genetic characterization of the H6N1 viruses. Sequence and phylogenetic analyses revealed that the H6N1 viruses possess seven gene segments that are closely related to those of the H5N1/97 viruses and that the H6 HA gene may have been of regional duck origin. The N1 NA has a 19-amino- acid deletion in the stalk characteristic of the N1 of H5N1/97 viruses, a feature possibly associated with adaptation to terrestrial poultry. Similar to the H5N1/97 viruses, these H6N1 viruses possess six human influenza virus-like amino acids in the PB2, NP and M2 proteins highlighting their enhanced potential for infecting humans. The marketing system of poultry in southeastern China which places poultry and humans in close proximity may enhance interspecies transmission of H6N1 viruses to humans. Co-circulation of H6N1 viruses with other precursors of the H5N1/97 virus, A/Goose/Guangdong/1/96 (H5N1)-like and A/Quail/HK/G1/97 (H9N2)-like viruses, in terrestrial poultry raises the possibility of the generation of H5N1/97-like viruses or other dangerous reassortants in this region. This possibility is reinforced by the isolation of a naturally occurring H6N1 reassortant virus from a pheasant with five H5N1/97-like gene segments (PB2, PB1, PA, NA and M). Moreover, analyses of the rates of amino acid substitution of the internal protein genes suggested that the H6N1 and H9N2 viruses might have been present in terrestrial poultry before the H5N1/97 outbreak in accordance with their apparent precursor role. In all, this thesis has shown that terrestrial poultry in southeastern China, particularly quail, are a reservoir for H6N1 viruses (increasingly so) in addition to H9N2 viruses. H6N1 alone has the potential to donate the seven requisite genes to generate an H5N1/97-like virus. It provided further evidence to uphold the hypothesis that southern China is an epicentre for the emergence of pandemic influenza viruses underscoring the importance of animal influenza virus surveillance there. Prospective action toward influenza pandemic preparedne

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