Id |
Subject |
Object |
Predicate |
Lexical cue |
T76 |
0-4 |
Sentence |
denotes |
3.1. |
T77 |
5-62 |
Sentence |
denotes |
Influenza A (H1–H16) Viruses Use Siaα2,3/2,6Gal Receptors |
T78 |
63-212 |
Sentence |
denotes |
HAs of H1–H16 viruses recognize specific sialyl glycans on the host epithelial cell surface, as a crucial step mediating virus infection (Figure 3a). |
T79 |
213-306 |
Sentence |
denotes |
IAVs from avians, either wild birds or domestic birds, typically prefer the α2,3Sia terminal. |
T80 |
307-472 |
Sentence |
denotes |
Surprisingly, a recent study showed that some gull/tern H16 viruses prefer α2,6Neu5Ac over or equal to the α2,3Neu5Ac terminal of synthetic sialylglycopolymers [23]. |
T81 |
473-826 |
Sentence |
denotes |
It was suggested that the particularly distinctive receptor-binding specificity of H16 viruses may be related to their HAs containing A138S (found in human 1977-derived H1N1 viruses, reducing binding to α2,3Neu5Ac receptors) and E190T (the amino acid (aa) at position 190 determining binding specificity of H1N1 viruses to the sialyl linkage type) [23]. |
T82 |
827-912 |
Sentence |
denotes |
Usually, viruses adapt to bind to sialyl glycans dominant in the host target tissues. |
T83 |
913-1224 |
Sentence |
denotes |
Information on virus collection from oral, nasal, nasopharyngeal, cloacal or feces swabs and sialyl glycan analysis of tissues of specific wild birds shedding the virus in the sample collection may lead to a better understanding of why some H16 viruses display binding distinct from that of other avian viruses. |
T84 |
1225-1378 |
Sentence |
denotes |
Binding preference for the internal part of sialyl glycans appears to differ among different viruses based on birds of isolation as indicated in Table 1. |
T85 |
1379-1598 |
Sentence |
denotes |
Several zoonotic influenza virus subtypes (Table 1) including avian subtypes H5N1, H7N9 and H9N2 and swine subtypes H1N1, H1N2 and H3N2 have been occasionally reported to cross the species barrier to infect humans [57]. |
T86 |
1599-1697 |
Sentence |
denotes |
However, human-to-human transmission of nonhuman viruses has been limited and non-sustained [154]. |
T87 |
1698-2014 |
Sentence |
denotes |
Viruses in four historical pandemics acquired strong binding to human-type α2,6Neu5Ac receptors for efficient human-to-human transmission [19,155,156,157]. (i) The H1N1 Spanish pandemic in 1918–1919 was found to include at least two strains with distinct receptor-binding properties during the pandemic period [155]. |
T88 |
2015-2158 |
Sentence |
denotes |
First, viral HAs have a single aa substitution, E190D, in the receptor-binding site (RBS) and bind to both avian-type and human-type receptors. |
T89 |
2159-2387 |
Sentence |
denotes |
Second, there are two aa substitutions in the HA RBS, E190D and G225D, that enable HA adaptation to bind only to α2,6Neu5Ac receptors. (ii) The H2N2 Asian pandemic in 1957–1958 had virus isolates from two stages of the pandemic. |
T90 |
2388-2789 |
Sentence |
denotes |
In the early pandemic stage, virus isolates can be divided into three subpopulations based on receptor binding specificities: avian-like viruses with 226Q and 228G in the HA RBS, atypical viruses with Q226L and 228G, and classic human viruses with Q226L and G228S that have preferential binding to avian-type receptors, both avian-type and human-type receptors, and human-type receptors, respectively. |
T91 |
2790-3416 |
Sentence |
denotes |
In the subsequent stage, all virus isolates have Q226L and G228S substitutions with preferential binding to human-type receptors [156]. (iii) The virus in the H3N2 Hong Kong pandemic in 1968–1969 had the same acquisition of Q226L and G228S substitutions in the HA RBS as that in the H2 pandemic for switching from avian-type to human-type receptor binding preference [157]. (iv) The virus in the H1N1 swine pandemic in 2009–2010 had 190D and 225D in the HA RBS as in the swine H1 HA RBS recognizing human-type α2,6Neu5Ac receptors that are abundant in the porcine lung, which is the main site of swine IAV replication [19,39]. |
T92 |
3417-3643 |
Sentence |
denotes |
Protein engineering by chimeragenesis and site-directed mutagenesis of H1 proteins suggested that A200T and A227E substitutions in the H1 swine pandemic were responsible for efficient and sustained human-to-human transmission. |
T93 |
3644-3838 |
Sentence |
denotes |
Molecular modeling revealed hydrogen bond formation between T200 and Q191 in the 190-helix that is important for receptor binding preference of H1 HAs and between E227 and Gal next to Sia [158]. |
T94 |
3839-4066 |
Sentence |
denotes |
Based on historical data, after a pandemic virus continued to circulate as a seasonal strain, the preexisting seasonal virus, which donated at least three gene segments to the pandemic virus, disappeared from human circulation. |
T95 |
4067-4371 |
Sentence |
denotes |
The disappearance of 1918-derived H1N1, 1957-derived H2N2 and 1977-derived H1N1 (being the 1918-derived H1N1, recurrent from a research laboratory in 1977, same as the classical swine H1N1 viruses) [159] has resulted in only 1968-derived H3N2 and 2009-derived H1N1 viruses remaining in human circulation. |
T96 |
4372-4694 |
Sentence |
denotes |
Despite binding to human-type receptors being essential for influenza virus transmission among humans, the binding of 1968-derived H3N2 viruses to the human-type receptor analog α2,6 sialyl N-acetyllactosamine (6′SLN)-polyacrylamide started to decrease significantly in 2001 and seemed to be completely lost in 2010 [160]. |
T97 |
4695-4998 |
Sentence |
denotes |
However, after the discovery [161] and the widespread use of long α2,6 sialylated N-glycans with multiple LN repeats for studies on influenza virus binding specificity, it appeared that 1968-derived H3N2 viruses have evolved binding preference for human-type receptors with LacNAc (LN) repeats [60,162]. |
T98 |
4999-5162 |
Sentence |
denotes |
Based on the binding preferences to short 3′SLN and 6′SLN and long 3′SLNLNLN and 6′SLNLNLN linked to a polyglutamic acid, IAVs can be divided into two groups [19]. |
T99 |
5163-5307 |
Sentence |
denotes |
Group 1 are avian viruses, including H5N1 and H5N3 viruses, that preferentially bind to terminal α2,3Neu5Ac with either short or long LN chains. |
T100 |
5308-5443 |
Sentence |
denotes |
Group 2 consists of viruses that preferentially bind to terminal α2,6Neu5Ac, and the viruses can be further divided into two subgroups. |
T101 |
5444-5571 |
Sentence |
denotes |
Subgroup 2-1 includes swine H1N2/2008 and pdm H1N1/2009 viruses, which can bind to both short and long α2,6 sialylated glycans. |
T102 |
5572-5682 |
Sentence |
denotes |
These results support the hypothesis that pigs are vessels to generate viral HAs with pandemic potential [41]. |
T103 |
5683-6026 |
Sentence |
denotes |
However, the pdm H1N1/2009 viruses acquired at least two amino acids that are different from the swine H1 HA, A200T and A227E, and they are responsible for the binding differences in fetuin, chicken erythrocytes and human erythrocytes and are believed to be determinants of the shift in binding specificity from swine-type to human-type [158]. |
T104 |
6027-6279 |
Sentence |
denotes |
Further investigation to find the α2,6 sialyl glycan structure that is able to clearly distinguish binding specificity between swine and pandemic viruses is needed since such sialyl glycans could be useful for surveillance and prevention of a pandemic. |
T105 |
6280-6479 |
Sentence |
denotes |
Subgroup 2-2 consists of long-term circulating human viruses including human H3N2/2008 viruses and human H1N1/2004 and H1N1/2006 viruses, which have binding preference to the long α2,6 sialyl glycan. |
T106 |
6480-6967 |
Sentence |
denotes |
Structural comparison of avian-type and human-type receptors interacting with the receptor binding sites of avian H3/1963, pandemic (pdm) H3/1968 and human H3/2007 (Figure 3b) revealed that trisaccharide Neu5Acα2,3Galβ1,3GlcNAc of lactoseries tetrasaccharide a (LSTa) interacts with the avian H3/1963 binding site in a cone-like topology (1mqm [149]), whereas 6′SLNLN interacts with pandemic H3/1968 (6tzb [150]) and human H3/2007 binding sites in an umbrella-like topology (6aov [151]). |
T107 |
6968-7053 |
Sentence |
denotes |
Residues 226 and 228 are important in determining sialyl linkage binding specificity. |
T108 |
7054-7373 |
Sentence |
denotes |
As shown in Figure 3b, Q226 in the avian H3/1963 binding site directly forms hydrogen bonds with Sia-1 and Gal-2 of LSTa, whereas S228 in the pdm H3/1968 binding site directly forms a hydrogen bond with Sia-1 of 6′SLNLN and S228 in the human H3/2007 binding site directly forms two hydrogen bonds with Sia-1 of 6′SLNLN. |
T109 |
7374-7552 |
Sentence |
denotes |
Although no direct interaction of residue 226 in pdm and human H3 HAs was found, a previous study suggested that L226Q mutation in the HA decreases α2,6Neu5Ac binding preference. |
T110 |
7553-7651 |
Sentence |
denotes |
Both G228 and S228 can be found in H3 avian HAs, whereas only S228 is found in human H3 HAs [149]. |
T111 |
7652-7792 |
Sentence |
denotes |
L226 is not conserved during circulation in humans; L226V and V226I substitutions were observed before 2001 and in 2004, respectively [160]. |
T112 |
7793-8172 |
Sentence |
denotes |
Similar to the H1 HA receptor binding site [10], two sets of human receptor binding residues provide networks to make contact with the long human-type receptor that results in an umbrella-like topology of the receptor. (i) A base region Neu5Acα2,6Galβ1- motif is governed by residues 131–138 in a 130-loop, residues 140–145 in a 140-loop and residues 219–228 in a 220-loop [163]. |
T113 |
8173-8317 |
Sentence |
denotes |
Figure 3b shows direct H-bond formation between Y98, G135, S136, N137, H183, E190 and S228 in the pdm H3/1968 binding site and Sia-1 of 6′SLNLN. |
T114 |
8318-8728 |
Sentence |
denotes |
In the human H3/2007 binding site, Y98, T135, S136, S137, S228, R222, and N225 make direct H-bonds with Sia-1 and Gal-2, respectively, of 6′SLNLN. (ii) The extension region -4GlcNAcβ1,4Galβ1,4GlcNAc motif is governed by residues 190–196 in a 190-helix and residues 156–160 in a 150-loop [163], and S193 and K156 in the pdm H3/1968 binding site were observed to generate direct H-bonds with GlcNAc-5 of 6′SLNLN. |
T115 |
8729-8816 |
Sentence |
denotes |
Amino acid change in HA during co-evolution with humans occurs to evade human immunity. |
T116 |
8817-9117 |
Sentence |
denotes |
Not only is there a change in antigenicity but the number of glycosylation sites masking antigenicity also increases over time as shown in Figure 3c; the numbers of glycosylation sites/monomer are two for avian H3/1968 HA, two for pdm H3/1968 HA, seven for human H3/2007 HA and six for human H3/2014. |
T117 |
9118-9315 |
Sentence |
denotes |
The limitation of increase in the number of glycosylation sites might be because the change of the virus must have a balance between mutation and selection for optimal immune evasion and infection. |
T118 |
9316-9632 |
Sentence |
denotes |
Taken together, the change in receptor binding specificity of long-term circulating human IAVs from short and long to long α2,6 sialylated glycans may have resulted from aa change in the RBS (Figure 3b,d) and an increase in glycosylation sites surrounding the RBS, possibly making the shallow RBS deeper (Figure 3c). |
T119 |
9633-9857 |
Sentence |
denotes |
The differences in receptor binding preferences of avian, pandemic and long-term circulating human IAVs are associated with viral pathology along the human respiratory tract containing different sialylated glycan structures. |
T120 |
9858-10159 |
Sentence |
denotes |
The preferential binding of avian and pandemic viruses to both short and extended receptors can typically cause diffuse alveolar damage, resulting in greater severity than that caused by long-term circulating human viruses with preference for long receptors that rarely infect human alveoli [164,165]. |
T121 |
10160-10269 |
Sentence |
denotes |
This correlates well with our finding that human alveolar N-glycans consist of mainly short receptors, 22.32: |
T122 |
10270-10275 |
Sentence |
denotes |
0.17: |
T123 |
10276-10282 |
Sentence |
denotes |
16.10: |
T124 |
10283-10307 |
Sentence |
denotes |
0.15 mol% (Neu5Acα2,3LN: |
T125 |
10308-10339 |
Sentence |
denotes |
Neu5Acα2,3(α1,3fucosylated LN): |
T126 |
10340-10353 |
Sentence |
denotes |
Neu5Acα2,6LN: |
T127 |
10354-10408 |
Sentence |
denotes |
Neu5Ac-LN-LN), of total human alveolar N-glycans [19]. |
T128 |
10409-10661 |
Sentence |
denotes |
Sialyl N-glycans with various numbers of LN units (up to 10 units) have been reported in human lungs (principally terminated in α2,3Neu5Ac [166]) and the human bronchus, whereas fewer extended LN profiles can be detected in the human nasopharynx [167]. |
T129 |
10662-10865 |
Sentence |
denotes |
Although structures of glycans in the human trachea have not be determined, the pdm H1N1/2009 virus was found at higher levels in tracheal aspirate specimens than in throat or nasopharyngeal swabs [168]. |
T130 |
10866-10955 |
Sentence |
denotes |
Uncomplicated long-term circulating human viruses are related to tracheobronchitis [169]. |