Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin

Wu, Nicholas C.; Xie, Jia; Zheng, Tianqing; Nycholat, Corwin M.; Grande, Geramie; Paulson, James C.; Lerner, Richard A.; Wilson, Ian A.

doi:10.1016/j.chom.2017.07.001

Cited by 24 publications

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“…Next, we performed two control experiments, in which we converted Lec2 terminal LacNAc into α2-6-sialyl LacNAc and sLe x . Consistent with our previous observations, HA-MTA exhibited decreased binding to Lec2 cells with newly installed α 2-6-sialic acids29 , but increased binding to Lec2 cells modified with sialyl Lewis X (sLe X )12 . These observations suggest that sequence flexibility of HK68-HA is capable to commit such viral α 1-2-fucoside preferences.Then, we developed an assay to assess if the newly addedα 1-2-fucosides have any impact on the IAV-mediated host killing.…”

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confidence: 91%

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hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection

Hong

Grande

et al. 2019

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AbstractHost cell-surface glycans play critical roles in influenza A virus (IAV) infection ranging from modulation of IAV attachment to membrane fusion and host tropism. Approaches for quick and sensitive profiling of the viral avidity towards a specific type of host-cell glycan can contribute to the understanding of tropism switching among different strains of IAV. In this study, we developed a method based on chemoenzymatic glycan engineering to investigate the possible involvement of α1-2-fucosides in IAV infections. Using a truncated human fucosyltransferase 1 (hFuT1), we were able to create α1-2-linked fucosides in situ on the host cell surface to assess their influence on the host cell binding to IAV hemagglutinin and the susceptibility of host cells toward IAV induced killing. We discovered that the newly added α1-2-fucosides on host cells enhanced the infection of several human pandemic IVA subtypes. These findings suggest that glycan epitopes other than sialic aicds should be taken into consideration for assessing the human pandemic risk of this viral pathogen.

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confidence: 91%

“…Using this assay, we tested the HA from A/HongKong/1/ 1968 (HK68) and its laboratory-derived HA-mutant strain HK68-MTA 29 Similar to HA binding results, infection by the wt HK68 was not affected by the addition of α 1-2-fucosides on the MDCK cell surface (Fig. 3C).…”

supporting

confidence: 54%

hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection

Hong

Grande

et al. 2019

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“…45 46 Epistatic interactions can shape the evolution of influenza viruses (3)(4)(5)(6). For 47 example, intragenic epistasis in HA has been suggested to limit the rate of 48 antigenic evolution and to inhibit the reversal of RBS substitutions to ancestral 49 genotypes (5)(6)(7)(8). An important question that remains unanswered is whether 50 the HA amino acid context in which a substitution occurs determines its ability 51 to escape from antibody recognition.…”

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confidence: 99%

Epistatic interactions can moderate the antigenic effect of substitutions in hemagglutinin of influenza H3N2 virus

Koel

Burke

Vliet

et al. 2018

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“…Of course, it is important to keep in mind that our maps only measure the effect single amino-acid mutations to BG505. Epistatic interactions among multiple mutations can play a role in viral fitness and immune evasion (Adams et al, 2017;Dahirel et al, 2011;Lynch et al, 2015b;Otsuka et al, 2018;Da Silva et al, 2010;Troyer et al, 2009;Wu et al, 2017). Similarly, we performed our experiments in the single genetic background of the BG505 Env, but the effects of mutations on viral growth and antigenicity sometimes differ among viral strains (Barton et al, 2016;Falkowska et al, 2014;Haddox et al, 2018).…”

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confidence: 99%

An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies

Dingens

Arenz²,

Weight³

et al. 2018

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Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus's Env protein and are themselves promising immunotherapeutics. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. While structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here we map how all single amino-acid mutations to Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites that are near but do not directly contact the antibody. The mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs' independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.

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Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin

Cited by 24 publications

References 0 publications

hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection

hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection

Epistatic interactions can moderate the antigenic effect of substitutions in hemagglutinin of influenza H3N2 virus

An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies

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