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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt
PLoS Pathogens, Volume 7, No. 5, Article e1002068, Year 2011
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Description
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. © 2011 Watanabe et al.
Available Materials
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https://efashare.b-cdn.net/share/pmc/articles/PMC3102706/bin/ppat.1002068.s006.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3102706/bin/ppat.1002068.s007.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3102706/bin/ppat.1002068.s008.ppt
https://efashare.b-cdn.net/share/pmc/articles/PMC3102706/bin/ppat.1002068.s009.ppt
Authors & Co-Authors
Watanabe, Yohei
Japan, Suita
Research Institute for Microbial Diseases
Ibrahim, Madiha Salah
Japan, Suita
Research Institute for Microbial Diseases
Egypt, Alexandria
Alexandria University
Egypt, Damanhour
Faculty of Veterinary Medicine
Ellakany, Hany F.
Egypt, Alexandria
Faculty of Veterinary Medicine
Kawashita, Norihito
Japan, Suita
Osaka University
Japan, Suita
Research Institute for Microbial Diseases
Mizuike, Rika
Japan, Suita
Research Institute for Microbial Diseases
Hiramatsu, Hiroaki
Japan, Kasugai
Chubu University
Sriwilaijaroen, Nogluk
Japan, Kasugai
Chubu University
Thailand, Pathum Thani
Faculty of Medicine, Thammasat University
Takagi, Tatsuya
Japan, Suita
Osaka University
Japan, Suita
Research Institute for Microbial Diseases
Suzuki, Yasuo
Japan, Kasugai
Chubu University
Ikuta, Kazuyoshi
Japan, Suita
Research Institute for Microbial Diseases
Statistics
Citations: 209
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1371/journal.ppat.1002068
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study
Study Locations
Egypt