Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread

Yen, Hui-Ling; Aldridge, Jerry R.; Boon, Adrianus C. M.; Ilyushina, Natalia A.; Salomon, Rachelle; Hulse-Post, D. J.; Marjuki, Henju; Franks, John; Boltz, David A.; Bush, Dorothy; Lipatov, A. S.; Webby, Richard J.; Rehg, Jerold E.; Webster, Robert G.

doi:10.1073/pnas.0811052106

Cited by 104 publications

(73 citation statements)

References 49 publications

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“…We also observed that Saudi H5N1 isolates possessed residues S120, D124, S129, Q138, R140, S141, N154, N155, T159, R162, R189 (H5 numbering) (Tables 2 and 3), described as important antigenic sites of clade 2.2 HPAI H5N1 viruses [27]. Several mutations found in the Saudi isolates have been previously reported to cause binding to a-2, 6 receptors and increased pathogenicity in mice [28,29]. In addition, some other amino acids (Y98, S136, W153, H183, E190, and L194) of the receptor-binding pocket that were identified among the isolates are known to bind preferentially to a-2,3-linked but not to a-2,6-linked sialic acids [22,30].…”

Section: Discussionsupporting

confidence: 63%

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

Al‐Qahtani

Mubin

Almajhdi

et al. 2015

J Infect Dev Ctries

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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.

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Section: Discussionsupporting

confidence: 63%

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

Al‐Qahtani

Mubin

Almajhdi

et al. 2015

J Infect Dev Ctries

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“…ing affinity and specificity of influenza virus HA (46,66,75,76,85). Referencing the crystal structure, the N81 side chain makes only localized contacts with L118 and Y120 on a nearby ␤-sheet, and based on its distance from the binding pocket, the mechanism by which the N81T mutation influences the receptor binding capacity is difficult to discern (81).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Influenza Virus Hemagglutinin Receptor Binding Mutants with Limited Receptor Recognition Properties and Conditional Replication Characteristics

Bradley

Galloway

Lasanajak

et al. 2011

J Virol

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To examine the range of selective processes that potentially operate when poorly binding influenza viruses adapt to replicate more efficiently in alternative environments, we passaged a virus containing an attenuating mutation in the hemagglutinin (HA) receptor binding site in mice and characterized the resulting mutants with respect to the structural locations of mutations selected, the replication phenotypes of the viruses, and their binding properties on glycan microarrays. The initial attenuated virus had a tyrosine-to-phenylalanine mutation at HA1 position 98 (Y98F), located in the receptor binding pocket, but viruses that were selected contained second-site pseudoreversion mutations in various structural locations that revealed a range of molecular mechanisms for modulating receptor binding that go beyond the scope that is generally mapped using receptor specificity mutants. A comparison of virus titers in the mouse respiratory tract versus MDCK cells in culture showed that the mutants displayed distinctive replication properties depending on the system, but all were less attenuated in mice than the Y98F virus. An analysis of receptor binding properties confirmed that the initial Y98F virus bound poorly to several different species of erythrocytes, while all mutants reacquired various degrees of hemagglutination activity. Interestingly, both the Y98F virus and pseudoreversion mutants were shown to bind very inefficiently to standard glycan microarrays containing an abundance of binding substrates for most influenza viruses that have been characterized to date, provided by the Consortium for Functional Glycomics. The viruses were also examined on a recently developed microarray containing glycans terminating in sialic acid derivatives, and limited binding to a potentially interesting subset of glycans was revealed. The results are discussed with respect to mechanisms for HA-mediated receptor binding, as well as regarding the species of molecules that may act as receptors for influenza virus on host cell surfaces.

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“…We hypothesize that specific strains of H1N1 and H5N1 may alter the stimulatory effects of HA on mDCs, because HA is considered a key determinant of influenza virus pathogenesis. It was reported that a minor change in the HA receptor domain is capable of modifying H5N1 virus virulence and systemic spread in mice (43). The 2009 pandemic H1N1 virus was recently found to trigger a form of pneumonia in ferrets more severe than that triggered by seasonal H1N1 virus but less severe than that triggered by the highly pathogenic avian influenza (HPAI) H5N1 virus (37), probably due to different HAs.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Activation by Recombinant Hemagglutinin Proteins of H1N1 and H5N1 Influenza A Viruses

Liu

Lin

et al. 2010

J Virol

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Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread

Cited by 104 publications

References 49 publications

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

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

Analysis of Influenza Virus Hemagglutinin Receptor Binding Mutants with Limited Receptor Recognition Properties and Conditional Replication Characteristics

Dendritic Cell Activation by Recombinant Hemagglutinin Proteins of H1N1 and H5N1 Influenza A Viruses

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