الفهرس 
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Abstract
Avian influenza virus H9N2 has been endemic in birds in the Middle East, in particular in Egypt with multiple cases of human infections since 1998. Despite concerns about the pandemic threat posed by H9N2, little is known about the biological properties of H9N2 in this epicenter of infection. Here, we evaluated the genetic compatibility and replication efficiency of reassortants between recent isolates of an Egyptian H5N1 and a H9N2 AIV (H5N1EGY and H9N2EGY). All internal viral proteins-encoding segments of the contemporaneous G1-like H9N2EGY, expressed individually and in combination in the genetic background of H5N1EGY. Influenza viruses utilize the viral polymerase complex, which is composed of PB1, PB2 and PA subunits, to replicate and transcribe the viral genome in the cell nucleus. Adaptation of viral polymerase is critical for efficient virus replication in a new host following cross-species transmission. Several adaptation markers in the polymerase have been identified among seasonal influenza viruses that are circulating in humans and avian influenza viruses, which cause sporadic human infections. The PB2 gene is one of the key determinants for the mammalian adaptation of avian influenza A viruses (IAVs). Although mammalian pathogenicity-related mutations (MPMs) in PB2 genes were identified in different genetic backgrounds of avian IAVs, the relative effects of single or multiple mutations on viral fitness could not be directly compared. This thesis work aimed to investigate the genetic compatibility and replication efficiency of reassortants, derived from recent avian influenza A/H5N1 and A/H9N2 viruses in vitro. So, we did Reverse Genetics (Rg) Systems for H5N1EGY and H9N2EGY and Generation of Reassortant, Mutant and Wild-type strains and determined the monocycle and multicycle replication efficiency of reassortant and wild-type strains in vitro. Our findings indicate that in the H5N1 virus, the PB2-Q591K mutation either alone or in combination with the PB2-E627K mutation, can strongly affect the viral replication efficiency and polymerase activity in mammalian systems in vitro, potentiating the zoonotic potential of these viruses and probably supporting their pandemic potential. Therefore, close monitoring of the circulating H9N2 and H5N1 with PB2-Q591K is mandatory and must be considered as viruses of concern.