Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt

PLoS Pathogens

Hany F. Ellakany¹  Norihito Kawashita²  Nogluk Sriwilaijaroen³  Yohei Watanabe³  Madiha S. Ibrahim³  Kazuyoshi Ikuta⁴  Hiroaki Hiramatsu⁵  Rika Mizuike⁶  Yasuo Suzuki⁷  Tatsuya Takagi⁷ 

[1] Department of Microbiology, Faculty of Veterinary Medicine, Alexandria University, Damanhour Branch, Egypt;Department of Poultry Diseases and Hygiene, Faculty of Veterinary Medicine, Alexandria University, Edfina Branch, Egypt;Department of Virology, Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka, Japan;Faculty of Medicine, Thammasat University (Rangsit Campus), PathumThani, Thailand;Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan;Health Scientific Hills, College of Life and Health Sciences, Chubu University, Aichi, Japan

关键词: H5N1;    Egypt;    Microbial mutation;    Sequence databases;    Influenza viruses;    Influenza A virus;    Birds;    Sequence analysis;   

DOI  :  10.1371/journal.ppat.1002068

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Highly pathogenic avian influenza A virus subtype H5N1 is currently widespread in Asia, Europe, and Africa, with 60% mortality in humans. In particular, since 2009 Egypt has unexpectedly had the highest number of human cases of H5N1 virus infection, with more than 50% of the cases worldwide, but the basis for this high incidence has not been elucidated. A change in receptor binding affinity of the viral hemagglutinin (HA) from α2,3- to α2,6-linked sialic acid (SA) is thought to be necessary for H5N1 virus to become pandemic. In this study, we conducted a phylogenetic analysis of H5N1 viruses isolated between 2006 and 2009 in Egypt. The phylogenetic results showed that recent human isolates clustered disproportionally into several new H5 sublineages suggesting that their HAs have changed their receptor specificity. Using reverse genetics, we found that these H5 sublineages have acquired an enhanced binding affinity for α2,6 SA in combination with residual affinity for α2,3 SA, and identified the amino acid mutations that produced this new receptor specificity. Recombinant H5N1 viruses with a single mutation at HA residue 192 or a double mutation at HA residues 129 and 151 had increased attachment to and infectivity in the human lower respiratory tract but not in the larynx. These findings correlated with enhanced virulence of the mutant viruses in mice. Interestingly, these H5 viruses, with increased affinity to α2,6 SA, emerged during viral diversification in bird populations and subsequently spread to humans. Our findings suggested that emergence of new H5 sublineages with α2,6 SA specificity caused a subsequent increase in human H5N1 influenza virus infections in Egypt, and provided data for understanding the virus's pandemic potential.

【 授权许可】

CC BY