Rescue of a H3N2 Influenza Virus Containing a Deficient Neuraminidase Protein by a Hemagglutinin with a Low Receptor-Binding Affinity

Richard, Mathilde; Erny, Alexandra; Caré, Bertrand; Traversier, Aurélien; Barthélémy, Mendy; Hay, Alan J.; Lin, Yi Pu; Ferraris, Olivier; Lina, Bruno

doi:10.1371/journal.pone.0033880

Cited by 22 publications

(19 citation statements)

References 23 publications

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“…There is a considerable literature pertaining to the need for “balance” between HA and NA activities of influenza viruses, the idea being that if the receptor specificity changes with a change in host, then the NA specificity must follow. There are many examples of adjustments to activity levels [14; 21; 24; 30; 32; 34] but the specificity shows only modest changes [2; 15] and the NA always has higher activity on α2-3 than α2-6 sialylated glycans as summarized in Supplementary Table 1 of a recent review [1]. A more recent report [32] shows less activity with MUN substrate for recombinant NA of pdmH1N1 strain A/California/4/2009 (Kcat 3 sec −1 , Km 373 μM) than for older strains Japan/57 and Hong Kong/68 (Kcat 29 and 18 sec −1 , Km 79 and 20 μM, respectively).…”

Section: Resultsmentioning

confidence: 99%

Glycan array analysis of influenza H1N1 binding and release

Gulati

Lasanajak

Smith

et al. 2014

CBM

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Influenza viruses initiate infection by attaching to sialic acid receptors on the surface of host cells. It has been recognized for some time that avian influenza viruses usually bind to terminal sialic acid that is linked in the α2-3 configuration to the next sugar while human viruses show preference for α2-6 linked sialic acid. With developments in synthetic chemistry and chemo-enzymatic methods of synthesizing quite complex glycans, it has become clear that the binding specificity extends beyond the sialic acid, and this has led to considerable interest in developing glycan reagents that could be used either as a diagnostic tool for particular influenza viruses, or to identify cells that are susceptible to infection by certain influenza viruses. Here we describe the use of the Consortium for Functional Glycomics Glycan Array to investigate binding specificity of influenza hemagglutinin and cleavage by neuraminidase, using seasonal and pandemic H1N1 influenza viruses as examples, and compare the results with published data using other array methods.

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Section: Resultsmentioning

confidence: 99%

Glycan array analysis of influenza H1N1 binding and release

Gulati

Lasanajak

Smith

et al. 2014

CBM

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“…In this vein, Blick et al reported that a zanamivir resistant virus incorporating an HA mutation that significantly impaired affinity, actually required the presence of the drug for viral growth, because returning functionality of the NA shifts the balance to overwhelming sialidase activity and HA cannot effectively complete the receptor binding and entry process [ 188 ]. Similarly, when NA is inherently defective, growth can be rescued by adaption of HA [ 189 , 190 , 191 , 192 , 193 ]. Baigent et al combined the study of HA glycosylation and NA stalk length, both characteristics found to change among transmission and adaptation, and illustrated a fine balance of the two modifications needed to sustain infection [ 67 ].…”

Section: Functional Balance Of Ha and Namentioning

confidence: 99%

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

Byrd-Leotis

Cummings

Steinhauer

2017

IJMS

170

140

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The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers. For example, avian viruses preferentially recognize α2,3-Sialic acid terminating glycans as receptors and mammalian viruses recognize α2,6-Sialic acid. The neuraminidase, or the receptor-destroying protein, cleaves the sialic acid from cellular membrane constituents and viral glycoproteins allowing for egress of nascent virions. A functional balance of activity has been demonstrated between the two glycoproteins, resulting in an optimum level of HA affinity and NA enzymatic cleavage to allow for productive infection. As more is understood about both HA and NA, the relevance for functional balance between HA and NA continues to expand, with potential implications for interspecies transmission, host adaptation, and pathogenicity.

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“…There may also be other uncertainties, for example, host range restriction of influenza virus replication in CEFs. [38][39][40][41] In Vivo Anti-influenza Virus Activity in Specific Pathogen Free (SPF) Chicken…”

Section: Inhibition Of Influenza Neuraminidasesmentioning

confidence: 99%

Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

et al. 2018

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Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five sub-series of oseltamivir derivatives were designed and synthesized to improve their activity towards drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidases (NAs). The bioassay results showed that compound 21h exhibited antiviral activities similar to or better than those of oseltamivir carboxylate (OSC) against H5N1, H5N2, H5N6 and H5N8. Besides, 21h was 5-to 86-fold more potent than OSC toward N1, N8, and N1-H274Y mutant NAs in the inhibitory assays. Computational studies provided a plausible rationale for the high potency of 21h against group-1 and N1-H274Y NAs. In addition, 21h demonstrated acceptable oral bioavailability, low acute toxicity and potent antiviral activity in vivo, and high metabolic stability. Overall, above excellent profiles make 21h a promising drug candidate for the treatment of influenza virus infection.

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Rescue of a H3N2 Influenza Virus Containing a Deficient Neuraminidase Protein by a Hemagglutinin with a Low Receptor-Binding Affinity

Cited by 22 publications

References 23 publications

Glycan array analysis of influenza H1N1 binding and release

Glycan array analysis of influenza H1N1 binding and release

The Interplay between the Host Receptor and Influenza Virus Hemagglutinin and Neuraminidase

Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

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