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80051673048
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note
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HAs cluster into two distinct groups on the basis of their primary sequence. Group 1 HAs include 10 of the 16 subtypes: H1, H2, H5, H6, H8, H9, H11, H12, H13, and H16. Group 2 HAs account for the remaining 6 subtypes: H3, H4, H7, H10, H14, and H15.
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80051671048
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note
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Materials and methods are available as supporting material on Science Online.
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28
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80051668030
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-
note
-
Although CR8020 binds to H4 and H14, the affinity is probably too low to result in in vitro neutralization, at least at the concentration tested here. In vitro neutralization of H14 and H15 viruses was not tested.
-
-
-
-
29
-
-
80051668616
-
-
note
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All increases in body weight were statistically significant (P ≤ 0.018), except for the H7N7 challenge group treated with 3mg/kg CR8020 (P = 0.168).
-
-
-
-
31
-
-
80051667102
-
-
note
-
The final model includes HA1 residues 11 to 328, HA2 residues 1 to 175, CR8020 heavy chain residues 2 to 222, and light chain residues 1 to 212. The asymmetric unit contains one HA protomer bound to one CR8020 Fab, with the additional protomers in the trimer generated by crystallographic symmetry operations.
-
-
-
-
32
-
-
80051666887
-
-
note
-
In this regard, CR8020 can be thought of as being analogous to the envelope antibodies to HIV 2F5, 4E10, and Z13. These antibodies recognize the membrane-proximal external region (MPER), a short helical peptide from the gp41 subunit that is closely associated with the viral envelope.
-
-
-
-
33
-
-
80051664418
-
-
note
-
154 in HA2, although the extent of the contribution of this interaction to the overall binding energy is unclear.
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34
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37849052232
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80051667558
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note
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Details of the data set and analysis can be found in the supporting online material on Science Online.
-
-
-
-
36
-
-
80051672609
-
-
note
-
In this analysis, residues are considered conserved if they fall within one of the following groups: Asp/Asn/Glu/Gln, Phe/Tyr, Ile/Leu/Val/Met, Lys/Arg, or Ser/Thr.
-
-
-
-
38
-
-
85101480185
-
-
note
-
19Asn mutations escape virus neutralization.
-
-
-
-
40
-
-
80051663507
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-
note
-
54 side chains.
-
-
-
-
41
-
-
85101443309
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-
note
-
19Asn substitutions in the H7 population (35).
-
-
-
-
42
-
-
85101477984
-
-
note
-
d for CR8020 binding is comparable with that of H7, which is neutralized.
-
-
-
-
43
-
-
80051666716
-
-
note
-
Neutralization of H14 viruses has not been tested, but comparable binding of CR8020 to H4 and H14 suggests that H14 will not be neutralized.
-
-
-
-
44
-
-
85101437740
-
-
note
-
325Gly mutation in HA1, which has a negligible effect on CR8020 binding in a HK68 background.
-
-
-
-
45
-
-
85101482415
-
-
note
-
38 and the more general and well-documented use of glycans to mask and unmask surfaces to evade immune recognition, such as vividly illustrated in the evolution of human H1N1 viruses (12, 56).
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46
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0028023726
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80051671457
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note
-
In contrast, a control mAb against the HA1 head bound to A/Wisconsin/67/2005 HA in all three conformations, and binding was only lost after DTT treatment, which dissociates HA1 from HA2 in the postfusion state.
-
-
-
-
48
-
-
80051663408
-
-
note
-
This is evidenced by the fact that, in this case, treatment with DTT did not diminish CR8057 binding to A/Wisconsin/67/2005 HA. In line with its narrow spectrum of neutralization (table S1), CR8057 did not bind to any conformation of the HAs of A/Hong Kong/1/1968 or A/Hong Kong/24/1985.
-
-
-
-
49
-
-
80051670892
-
-
note
-
Because the initial crystals only appeared between 3 and 7 days after the start of the experiment, CR8020 must be capable of retaining HA in the prefusion state for several days at low pH.
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51
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