Characterization of H5N1 influenza A virus that caused the first highly pathogenic avian influenza outbreak in Saudi Arabia

Abstract

Introduction: Saudi Arabia (SA) experienced a highly pathogenic avian influenza (HPAI) H5N1 outbreak in domesticated birds in 2007. Methodology: Forty-three hemagglutinin (HA) and 41 neuraminidase (NA) genes of HPAI H5N1 viruses were sequenced and phylogenetic analyses of completely sequenced genes were performed to compare with other viral HA and NA gene sequences available in the public databases. Results: Molecular characterization of the H5N1 viruses revealed two genetically distinct clades, 2.2.2 and 2.3.1, of H5N1 viruses circulating in the area. Amino acid sequence analysis of the HA gene indicated that the virus from 2.2.2 contained the sequence SPQGERRRK-R/G at the cleavage site, while the virus from 2.3.1 contained the sequence SPQRERRRK-R/G. Additionally, a few mutations with amino acid substitutions such as M226I at N-link glycosylation site were identified in two of these isolates. Amino acid sequence of the NA gene showed a 20-amino-acid deletion in the NA stalk region, required for enhanced virulence of influenza viruses and its adaptation from wild birds to domestic chickens. As close contact between humans and birds is unavoidable, there is a need for a thorough understanding of the virus epidemiology, factors affecting the spread of the virus, and molecular characterization such as phylogeny and substitution rates of H5N1 viruses circulating in the region. Conclusion: Two genetically distinct clades were found to be circulating in the country, which could likely result in recombination and emergence of more virulent viral strains. These findings could be helpful for the authorities devising control measures against these viruses.