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Basic Characteristics of Mutations
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Mutation Site
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W68X |
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Mutation Site Sentence
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NS1-gene mutations like Val236 Ala (DENV2) or Trp68 stop codon in DENV3 were associated with decreased NS1 production and secretion. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsense substitution |
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Gene/Protein/Region
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NS1 |
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Standardized Encoding Gene
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NS1
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Genotype/Subtype
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DENV-3 |
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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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- |
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Literature Information
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PMID
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35397074
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Title
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Non-structural protein 1 (NS1) variants from dengue virus clinical samples revealed mutations that influence NS1 production and secretion
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Author
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Ghosh A,Sukla S,Nath H,Saha R,De A,Biswas S
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Journal
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European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
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Journal Info
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2022 May;41(5):803-814
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Abstract
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Dengue diagnosis primarily relies on NS1 ELISA and serological (IgG/IgM) tests. There are reports of low and variable sensitivity of the widely used NS1 ELISA tests. Poor sensitivity has been attributed to patient's infection status, prevalent serotypes, and the geographical origin of the samples. We investigated whether NS1 mutations directly have any impact on NS1 ELISA-based dengue virus (DENV) detection in clinical samples. Fifty-eight serum samples were collected from dengue-endemic area during 2015-2017 and tested with three commonly used NS1 ELISA kits. The samples were subjected to diagnostic RT-PCR and sequencing of structural gene(s). Sequencing of NS1 gene revealed amino acid changes which were transferred to respective wild type NS1 backbone to determine their effects on NS1 production and secretion in Huh-7, Vero, and A549 cells. Eighty-seven percent samples were virus RNA-positive but 65% of these were NS1 ELISA-positive. NS1-gene mutations like Val236 Ala (DENV2) or Trp68 stop codon in DENV3 were associated with decreased NS1 production and secretion. These mutations were originally identified in NS1 ELISA-negative clinical isolates. All DENV1 and > 80% DENV2 were NS1 ELISA-positive. The three NS1 ELISA could not detect recently circulating DENV3 single infections despite being RNA-positive. Among serotypes 1-3, wild-type NS1 production was highest for DENV1 and lowest for DENV3 in all cell lines tested. Mutations in circulating DENV directly correlated with NS1 production and secretion and, hence, ELISA-based NS1 detection. Further studies to define more NS1 mutations in clinical samples are needed to optimize ELISA kits for more sensitive dengue diagnosis.
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Sequence Data
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MW269878
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