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Basic Characteristics of Mutations
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Mutation Site
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T90I |
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Mutation Site Sentence
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The MUT-Y273 virus in the recipient ferret had acquired a rare T90I HA substitution (contained in only 7 out of 7,373 strains in GISAID), as well as the NP, PA and PB1 genes from the WT-H273 virus, which differed by 4 amino acids compared to the MUT-Y273 virus (see Fig. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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HA |
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Standardized Encoding Gene
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HA
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Genotype/Subtype
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B/Yamagata |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Singapore |
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Literature Information
|
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PMID
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30201817
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Title
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Characterization of Influenza B Virus Variants with Reduced Neuraminidase Inhibitor Susceptibility
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Author
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Farrukee R,Zarebski AE,McCaw JM,Bloom JD,Reading PC,Hurt AC
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Journal
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Antimicrobial agents and chemotherapy
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Journal Info
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2018 Oct 24;62(11):e01081-18
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Abstract
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Treatment options for influenza B virus infections are limited to neuraminidase inhibitors (NAIs), which block the neuraminidase (NA) glycoprotein on the virion surface. The development of NAI resistance would therefore result in a loss of antiviral treatment options for influenza B virus infections. This study characterized two contemporary influenza B viruses with known resistance-conferring NA amino acid substitutions, D197N and H273Y, detected during routine surveillance. The D197N and H273Y variants were characterized in vitro by assessing NA enzyme activity and affinity, as well as replication in cell culture compared to those of NAI-sensitive wild-type viruses. In vivo studies were also performed in ferrets to assess the replication and transmissibility of each variant. Mathematical models were used to analyze within-host and between-host fitness of variants relative to wild-type viruses. The data revealed that the H273Y variant had NA enzyme function similar to that of its wild type but had slightly reduced replication and transmission efficiency in vivo The D197N variant had impaired NA enzyme function, but there was no evidence of reduction in replication or transmission efficiency in ferrets. Our data suggest that the influenza B virus variant with the H273Y NA substitution had a more notable reduction in fitness compared to wild-type viruses than the influenza B variant with the D197N NA substitution. Although a D197N variant is yet to become widespread, it is the most commonly detected NAI-resistant influenza B virus in surveillance studies. Our results highlight the need to carefully monitor circulating viruses for the spread of influenza B viruses with the D197N NA substitution.
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Sequence Data
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-
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