Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

Song, Hao; Qi, Jianxun; Xiao, Haixia; Bi, Yang; Zhang, Wei; Xu, Ying; Wang, Fei; Shi, Yi; Gao, George F.

doi:10.1016/j.celrep.2017.07.028

Cited by 64 publications

(64 citation statements)

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“…For example, Q226L and G228S were detected in HA protein of both H4N6 swine isolates but rarely in avian isolates, and these mutations increased human-like receptor binding ability and could have further enhanced virus transmission ability in pigs (Fig. 4) [33, 34]. In summary, this study suggested that tissue tropisms of H4N6 avian IAVs affect their spillovers from wild birds to pigs.…”

Section: Discussionmentioning

confidence: 82%

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Zhang

Cummingham²,

et al. 2020

Preprint

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32Wild aquatic birds maintain a large genetically diverse pool of influenza A viruses (IAVs), which can be 33 transmitted to lower mammals and ultimately humans. Through phenotypic analyses, only a small set of 34 avian IAVs replicated well in the epithelial cells of swine upper respiratory tracts, and these viruses were 35 shown to infect and cause virus shedding in pigs. Such a phenotypic trait appears to emerge randomly and 36 are distributed among IAVs across multiple avian species, geographic and temporal orders, and is 37 determined not by receptor binding preference but other markers across genomic segments, such as those 38 in the ribonucleoprotein complex. This study demonstrates that phenotypic variants exist among avian 39 IAVs, only a few of which may result in viral shedding in pigs upon infection, providing opportunities for 40 these viruses to become pig adapted, thus posing a higher potential risk for creating novel variants or 41 detrimental reassortants within pig populations. 42 43 44 45 46 47 Author Summary 49Having both avian-like receptors and human-like α2,6-linked sialic acid receptors, swine serve as a 50 "mixing vessel" for generating human influenza pandemic strains. All HA subtypes of IAVs can infect 51 swine; however, only sporadic cases of avian IAVs are reported in domestic swine. The molecular 52 mechanisms affecting avian IAVs ability to infect swine are still not fully understood. Through 53 phenotypic analyses, this study suggested that tissue tropisms (i.e., in swine upper respiratory tracts) of 54 avian IAVs affect their spillovers from wild birds to pigs, and this phenotype was determined not by 55 receptor binding preference but by other markers across genomic segments, such as those in the 56 ribonucleoprotein complex. In addition, our results showed that such a phenotypic trait was sporadically 57 and randomly distributed among IAVs across multiple avian species, geographic and temporal orders. 58This study suggested an efficient way for risk assessment of avian IAVs, such as in evaluating their 59 potentials to be transmitted from avian to pigs. 60 61 Influenza A viruses (IAVs), a member in the Orthomyxoviridae family, are a negative single stranded 63 RNA virus with eight gene segments, encoding at least 11 proteins. The nomenclatures of IAVs are 64 determined based on antigenic properties of two surface glycoproteins, Hemagglutinin (HA) and 65 Neuraminidase (NA). To date, 18 HA subtypes and 11 NA subtypes have been identified [1, 2]. Besides 66 humans, pigs, dogs, and horses, IAVs have been recovered from variety of bird species, including at least 67 105 wild bird species of 26 different families [3]. Among wild birds, birds of wetlands and aquatic 68 environments such as the Anseriformes (particularly ducks, geese, and swans) and Charadriiformes 69 (particularly gulls, terns, and waders) constitute the major natural IAV reservoir [4]. They maintain a 70 large IAV genetic pool, which contributes to the appearance of new IAVs in other birds, lower mammals, 71 and ultima...

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Section: Discussionmentioning

confidence: 82%

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Zhang

Cummingham²,

et al. 2020

Preprint

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“…In the evolving ways from avian to human tropism for H2-and H3-subtype IAVs, Q226L and G228S substitutions are key determinants, and the Q226L substitution appears to be more critical for human receptor recognition (Matrosovich et al, 2000;Rogers et al, 1983;Xu et al, 2010). Recent research revealed that Q226L substitution also plays a pivotal role in altering receptor-binding specificity for H4 HAs, and G228S substitution would decrease the affinity for avian receptors while enhancing binding to human receptors (Song et al, 2017). Although H5-subtype AIVs have not evolved a human receptor-binding preference in nature, several tropismswitching substitutions have been identified in laboratories The H7-SGTL mutant structures were superimposed with the structures of SH1-H7N9 HA in complex with avian (A and B) or human (C and D) receptor analogs for comparison.…”

Section: Discussionmentioning

confidence: 99%

Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin

Peng

Zhang

et al. 2019

Cell Reports

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“…How other HA subtypes switch receptor specificity from α2,3-linked sialic acid to α2,6-linked sialic acid has also been studied. Different subtypes appear to require different sets of mutations to switch specificity toward α2,6-linked sialic acid-Q226L/ G228S for H4 HA (Song et al 2017), G225D for H6 HA (de Vries et al 2017b), V186G/K193T/ G228S, V186K/K193T/G228S or V186N/ N224K/G228S for H7 HA (de Vries et al 2017a), and K158aA/D193T/Q226L/G228S for H10 HA (Tzarum et al 2017) ("158a" indicates the insertion of an amino acid after position 158). Because of the structural variability of the RBS in different HA subtypes, it is not surprising that the mutational requirements for switching receptor specificity are different for different subtypes.…”

Section: Receptor Binding and Specificity Of Hemagglutininmentioning

confidence: 99%

Influenza Hemagglutinin Structures and Antibody Recognition

Wilson

2019

Cold Spring Harb Perspect Med

130

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Hemagglutinin (HA) is most abundant glycoprotein on the influenza virus surface. Influenza HA promotes viral entry by engaging the receptor and mediating virus-host membrane fusion. At the same time, HA is the major antigen of the influenza virus. HA antigenic shift can result in pandemics, whereas antigenic drift allows human circulating strains to escape herd immunity. Most antibody responses against HA are strain-specific. However, antibodies that have neutralizing activities against multiple strains or even subtypes have now been discovered and characterized. These broadly neutralizing antibodies (bnAbs) target conserved regions on HA, such as the receptor-binding site and the stem domain. Structural studies of such bnAbs have provided important insight into universal influenza vaccine and therapeutic design. This review discusses the HA functions as well as HA-antibody interactions from a structural perspective.

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Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

Cited by 64 publications

References 50 publications

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Tissue tropisms of avian influenza A viruses affect their spillovers from wild birds to pigs

Avian-to-Human Receptor-Binding Adaptation of Avian H7N9 Influenza Virus Hemagglutinin

Influenza Hemagglutinin Structures and Antibody Recognition

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