Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid

Reiter‐Scherer, Valentin; Cuellar-Camacho, José Luis; Bhatia, Sumati; Haag, Rainer; Herrmann, Andreas; Lauster, Daniel; Rabe, Jürgen P.

doi:10.1016/j.bpj.2019.01.041

Cited by 36 publications

(54 citation statements)

References 69 publications

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“…Although HA plays a crucial role in receptor binding and concurrent mutation capabilities, NA also has a key role in removing sialic acids from cellular receptors and from the new HA and NA on budding virions, which are sialylated as part of the glycosylation processes within the host cell ( 67 ). A balance between HA and NA is essential for viral fitness.…”

Section: Receptor Binding Of Virusesmentioning

confidence: 99%

Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses

2020

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The 2019 novel coronavirus (SARS-CoV-2) pandemic has caused a global health emergency. The outbreak of this virus has raised a number of questions: What is SARS-CoV-2? How transmissible is SARS-CoV-2? How severely affected are patients infected with SARS-CoV-2? What are the risk factors for viral infection? What are the differences between this novel coronavirus and other coronaviruses? To answer these questions, we performed a comparative study of four pathogenic viruses that primarily attack the respiratory system and may cause death, namely, SARS-CoV-2, severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and influenza A viruses (H1N1 and H3N2 strains). This comparative study provides a critical evaluation of the origin, genomic features, transmission, and pathogenicity of these viruses. Because the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 is ongoing, this evaluation may inform public health administrators and medical experts to aid in curbing the pandemic's progression.

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Section: Receptor Binding Of Virusesmentioning

confidence: 99%

Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses

2020

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“…It has recently been reported that NA also enables virus movement on the cell surface toward endocytic sites, resulting in virus internalization for infection (14,15). Since both proteins target the same receptor, the functional activities of HA and NA need to be balanced for both virus entry into and virus release from host cells (16).…”

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confidence: 99%

H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity

Arai

Elgendy

Daidoji

et al. 2020

J Virol

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Some avian influenza (AI) viruses have a deletion of up to 20-30 amino acids in their NA stalk. This has been associated with changes in virus replication and host range. Currently prevalent H9N2 AI viruses only have a 2 or 3 amino acid deletion, which were detected in G1 and Y280 lineage viruses, respectively. The effect of an NA deletion on the H9N2 phenotype has not been fully elucidated. In this study, we isolated G1 mutants that carried an 8 amino acid deletion in their NA stalk. To systematically analyze the effect of NA stalk length and concomitant (de)glycosylation on G1 replication and host range, we generated G1 viruses with various NA stalk lengths and were either glycosylated or not glycosylated. The stalk length was correlated with NA sialidase activity, using low molecular weight substrates, and with virus elution efficacy from erythrocytes. G1 virus replication in avian cells and eggs was positively correlated with NA stalk length, but was negatively correlated in human cells and mice. NA stalk length modulated G1 virus entry in host cells, with shorter stalks enabling more efficient G1 entry into human cells. However, with an HA with higher α2,6 Sia affinity, the effect of NA stalk length on G1 virus infection was reversed, with shorter NA stalks reducing virus entry into human cells. These results indicated that that a balance between HA binding affinity and NA sialidase activity, modulated by NA stalk length, was required for optimal G1 virus entry into human airway cells. IMPORTANCE H9N2 avian influenza (AI) virus, one of the most prevalent AI viruses, has caused repeated poultry and human infections, posing a huge public health risk. The H9N2 virus has diversified into multiple lineages, with the G1 lineage most prevalent worldwide. In this study, we isolated G1 variants carrying an 8 amino acid deletion in their NA stalk, which was, to our knowledge, the longest deletion found in H9N2 viruses in the field. NA stalk length was found to modulate G1 virus entry into host cells, with the effects being species-specific and dependent on the corresponding HA binding affinity. Our results suggested that, in nature, H9N2 G1 viruses balance their HA and NA functions by the NA stalk length, leading to the possible association of host range and virulence in poultry and mammals during the evolution of G1 lineage viruses.

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“…In the absence of catalytic activity, NA can bind sialic acid with similar or even higher affinity compared to HA. [70,71] The receptor-binding function and the receptor-cleaving function of these two glycoproteins must be balanced for efficient transmission and proliferation of the virus. [3,4,72] This functional balance is also reflected in the evolution of HA and NA.…”

Section: The Influence Of Neuraminidase On Bindingmentioning

confidence: 99%

A Dynamic, Supramolecular View on the Multivalent Interaction between Influenza Virus and Host Cell

Overeem

Vries

Huskens

2021

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Understanding how influenza viruses traverse the mucus and recognize host cells is critical for evaluating their zoonotic potential, and for prevention and treatment of the disease. The surface of the influenza A virus is covered with the receptor‐binding protein hemagglutinin and the receptor‐cleaving enzyme neuraminidase, which jointly control the interactions between the virus and the host cell. These proteins are organized in closely spaced trimers and tetramers to facilitate multivalent interactions with sialic acid‐terminated glycans. This review shows that the individually weak multivalent interactions of influenza viruses allow superselective binding, virus‐induced recruitment of receptors, and the formation of dynamic complexes that facilitate molecular walking. Techniques to measure the avidity and receptor specificity of influenza viruses are reviewed, and the pivotal role of multivalent interactions with their emergent properties in crossing the mucus and entering host cells is discussed. A model is proposed for the initiation of cell entry through virus‐induced receptor clustering. The multivalent interactions of influenza viruses are maintained in a dynamic regime by a functional balance between binding and cleaving.

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Force Spectroscopy Shows Dynamic Binding of Influenza Hemagglutinin and Neuraminidase to Sialic Acid

Cited by 36 publications

References 69 publications

Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses

Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses

H9N2 Influenza Virus Infections in Human Cells Require a Balance between Neuraminidase Sialidase Activity and Hemagglutinin Receptor Affinity

A Dynamic, Supramolecular View on the Multivalent Interaction between Influenza Virus and Host Cell

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