Influenza virus neuraminidase: Structure, antibodies, and inhibitors

Colman, Peter M.

doi:10.1002/pro.5560031007

Cited by 317 publications

(233 citation statements)

References 65 publications

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“…NA 315 appears to be near the vicinity of the active site of NA but this position is not directly associated with previously identified sites responsible for sialidase activity (SI Appendix, Fig. S3B) (17). Viral RNA samples directly prepared from the daily nasal washes collected from all inoculated (donor) and RD-infected ferrets were additionally analyzed.…”

Section: Identification Of Molecular Markers Associated With Pathogenmentioning

confidence: 99%

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Pascua

Song

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA 225G and NA 315N substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA 225G and NA 315N as potential virulence markers in mammals.

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Section: Identification Of Molecular Markers Associated With Pathogenmentioning

confidence: 99%

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Pascua

Song

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…NA plays an important role in liberating the bond between the virus and the host cell by specifically cleaving N-acetyl neuraminic acid (Neu5Ac) from its attachment to glycoconjugates on the cell surface (Colman, 1994). Thus, it is of interest to investigate natural viral isolates for variant NAs and also the influences of such variants on the susceptibility of H5N1 to NAIs.…”

Section: Introductionmentioning

confidence: 99%

The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern

Schaduangrat

Phanich

Rungrotmongkol

et al. 2016

Journal of General Virology

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Viral adaptability and survival arise due to the presence of quasispecies populations that are able to escape the immune response or produce drug-resistant variants. However, the presence of H5N1 virus with natural mutations acquired without any drug selection pressure poses a great threat. Cloacal samples collected from the 2004-2005 epidemics in Thailand from Asian open-billed storks revealed one major and several minor quasispecies populations with mutations on the oseltamivir (OTV)-binding site of the neuraminidase gene (NA) without prior exposure to a drug. Therefore, this study investigated the binding between the NA-containing novel mutations and OTV drug using molecular dynamic simulations and plaque inhibition assay. The results revealed that the mutant populations, S236F mutant, S236F/C278Y mutant, A250V/V266A/P271H/G285S mutant and C278Y mutant, had a lower binding affinity with OTV as compared with the WT virus due to rearrangement of amino acid residues and increased flexibility in the 150-loop. This result was further emphasized through the IC 50 values obtained for the major population and WT virus, 104.74 nM and 18.30 nM, respectively. Taken together, these data suggest that H5N1 viruses isolated from wild birds have already acquired OTV-resistant point mutations without any exposure to a drug.

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“…Neuraminidase cleaves sialic acid from these glycoconjugates, thereby liberating the influenza virus to allow it to spread the infection to new host cells (for review, see ref. 27). A mixedcharge cluster is identified in the structure.…”

mentioning

confidence: 99%

Clusters of charged residues in protein three-dimensional structures.

Zhu

Karlin²

1996

Proc. Natl. Acad. Sci. U.S.A.

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Table 2 we discuss the possible role of the charge clusters with respect to protein structure and function. We apply the methods described in our companion paper (1) with the objective to identify statistically significant charge clusters in protein three-dimensional (3D) structures and to suggest correlations with protein structure and function. A linear sequence or 3D-charge cluster signifies an anomalous distribution of the charged residues in a protein constituting one or more regions with excessive concentrations of charge relative to the overall charge composition of the protein.

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Influenza virus neuraminidase: Structure, antibodies, and inhibitors

Cited by 317 publications

References 65 publications

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern

Clusters of charged residues in protein three-dimensional structures.

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