Thesis (Ph.D.) - Cairo University - Faculty of Agriculture - Department of Microbiology

Highly pathogenic H5-subtype avian influenza viruses (HPAIV) heavily circulated in poultry in Egypt since 2006, leading to multiple poultry outbreaks and major intermittent human infections. The massive distribution of these viruses in domestic poultry resulted in numerous evolutionary changes with dramatic impact on transmissibility to mammals like humans. The transmitted viruses are either (1) well adapted to quickly infect mammals in their avian hosts, or (2) adapted to enhance their health in the new mammalian hosts. Not all of these adaptive differences are recognized or described thoroughly. Here, the impact of specific adaptive amino acid (aa) changes in the hemagglutinin of 2014-2015 H5N1, a dramatic avian influenza flu season in Egypt, has been investigated. To minimize the effort to deduce the contribution of specific adaptive mutation in the zoonosis process of HPAIV H5N1 subtype, an information spectrum-based phylogenetic algorithm, hereafter referred to as ISM, was applied. ISM was applied to analyze the affinity of Egyptian AIV isolate H5-type HA proteins (2006-2015) to human-type cell receptors. Recombinant IV expressing monobasic, low pathogenic (LP) H5-HA versions in the context of human influenza virus A/PR/8/1934(H1N1) (LP 7+1) were developed to characterize AIV H5-HA proteins with high ISM values indicating an increased HA trend towards human type receptors. Interestingly, using ISM analysis, we identified a LP 7+1 virus (LP-S10739C) expressing the monobasic H5-HA of AIV A/chicken/Egypt/S10739C/2015(H5N1) that showed high affinity towards human type receptors. This in silico prediction was reflected by a higher in vitro replication efficiency in mammalian cell cultures and higher virulence in mice compared to LP-7271

Issued also as CD