Substrate specificity of avian influenza H5N1 neuraminidase

Onsirisakul, Naruthai; Nakakita, Shin‐ichi; Boonarkart, Chompunuch; Kongchanagul, Alita; Suptawiwat, Ornpreya; Puthavathana, Pilaipan; Chaichuen, Krisada; Kittiniyom, Kanokwan; Suzuki, Yasuo; Auewarakul, Prasert

doi:10.5501/wjv.v3.i4.30

WJV

2014

DOI: 10.5501/wjv.v3.i4.30

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Substrate specificity of avian influenza H5N1 neuraminidase

Naruthai Onsirisakul

Shin‐ichi Nakakita

Chompunuch Boonarkart

et al.

Abstract: fluorescence Amplex Red assay. This method can identify the preference of α2,6-linked sialic acid or α2,3-linked sialic acid. Moreover, to avoid the bias of input virus, reverse genetic virus using NA gene from human isolated H5N1 were generated and used to compare with the seasonal influenza virus. Lastly, the substrate specificity profile was further confirmed by high-performance liquid chromatography (HPLC) analysis of the enzymatic product. RESULTS:The H5N1 NA showed higher activity on α2,3-linked sialic a… Show more

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Cited by 2 publications

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Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review

Munoz¹,

Nardi²,

Meulen

et al. 2015

EcoHealth

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In December 2011, the European Food Safety Authority awarded a Grant for the implementation of the FLURISK project. The main objective of FLURISK was the development of an epidemiological and virological evidence-based influenza risk assessment framework (IRAF) to assess influenza A virus strains circulating in the animal population according to their potential to cross the species barrier and cause infections in humans. With the purpose of gathering virological data to include in the IRAF, a literature review was conducted and key findings are presented here. Several adaptive traits have been identified in influenza viruses infecting domestic animals and a significance of these adaptations for the emergence of zoonotic influenza, such as shift in receptor preference and mutations in the replication proteins, has been hypothesized. Nonetheless, and despite several decades of research, a comprehensive understanding of the conditions that facilitate interspecies transmission is still lacking. This has been hampered by the intrinsic difficulties of the subject and the complexity of correlating environmental, viral and host factors. Finding the most suitable and feasible way of investigating these factors in laboratory settings represents another challenge. The majority of the studies identified through this review focus on only a subset of species, subtypes and genes, such as influenza in avian species and avian influenza viruses adapting to humans, especially in the context of highly pathogenic avian influenza H5N1. Further research applying a holistic approach and investigating the broader influenza genetic spectrum is urgently needed in the field of genetic adaptation of influenza A viruses.

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Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review

Munoz¹,

Nardi²,

Meulen

et al. 2015

EcoHealth

View full text Add to dashboard Cite

show abstract

Glycan binding and specificity of viral influenza neuraminidases by classical molecular dynamics and replica exchange molecular dynamics simulations

Phanich

Threeracheep

Kungwan

et al. 2018

Journal of Biomolecular Structure and Dynamics

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Two important glycoproteins on the influenza virus membrane, hemagglutinin (HA) and neuraminidase (NA), are relevant to virus replication. As previously reported, HA has a substrate specificity towards SIA-2,3-GAL-1,4-NAG (3SL) and SIA-2,6-GAL-1,4-NAG (6SL) glycans, while NA can cleave both types of linkages. However, the substrate binding into NA and its preference are not well understood. In this work, the glycan binding and specificity of human and avian NAs were evaluated by classical molecular dynamics (MD) simulations, whilst the conformational diversity of 3SL avian and 6SL human glycans in an unbound state was investigated by replica exchange MD simulations. The results indicated that the 3SL avian receptor fits well in the binding cavity of all NAs and does not require a conformational change for such binding compared to the flexible shape of the 6SL human receptor. From the QM/MM-GBSA binding free energy and decomposition free energy data, 6SL showed a much stronger binding towards human NAs (H1N1, H2N2 and H3N2) than to avian NAs (H5N1 and H7N9). This suggests that influenza NAs have a substrate specificity corresponding to their HA, indicating the functional balance between the two important glycoproteins. Both linkages show distinct glycan topologies when complexed with NAs, while the flexibility of torsion angles between GAL and NAG in 6SL results in the various shapes of glycan and different binding patterns. Lower conformational diversities of both glycans when bound to NA compared to the unbound state were found, and were required in order to be accommodated within the NA cavity. Communicated by Ramaswamy H. Sarma.

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Substrate specificity of avian influenza H5N1 neuraminidase

Cited by 2 publications

References 36 publications

Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review

Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review

Glycan binding and specificity of viral influenza neuraminidases by classical molecular dynamics and replica exchange molecular dynamics simulations

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