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Basic Characteristics of Mutations
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Mutation Site
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K356Q |
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Mutation Site Sentence
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Another BAY 57-1293-resistant UL5 mutant (Lys356Gln), which showed faster growth characteristics in cell culture, however, was at least equally virulent compared to the parent strain. |
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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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UL5 |
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Standardized Encoding Gene
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UL5
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Genotype/Subtype
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- |
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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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Herpes simplex
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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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BAY 57-1293 |
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Location
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- |
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Literature Information
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PMID
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18539344
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Title
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Mutations close to functional motif IV in HSV-1 UL5 helicase that confer resistance to HSV helicase-primase inhibitors, variously affect virus growth rate and pathogenicity
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Author
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Biswas S,Tiley LS,Zimmermann H,Birkmann A,Field HJ
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Journal
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Antiviral research
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Journal Info
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2008 Oct;80(1):81-5
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Abstract
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Herpes simplex virus (HSV) helicase-primase (HP) is the target for a novel class of antiviral compounds, the helicase-primase inhibitors (HPIs), e.g. BAY 57-1293. Although mutations in herpesviruses conferring resistance to nucleoside analogues are commonly associated with attenuation in vivo, to date, this is not necessarily true for HPIs. HPI-resistant HSV mutants selected in tissue culture are reported to be equally pathogenic compared to parental virus in animal models. Here we demonstrate that a slow-growing HSV-1 mutant, with the BAY 57-1293-resistance mutation Gly352Arg in UL5 helicase, is clearly less virulent than its wild-type parent in a murine zosteriform infection model. This contrasts with published results obtained for a mutant containing a different HPI-resistance substitution (Gly352Val) at the same location, since this mutant was reported to be fully pathogenic. We believe our report to be the first to describe an HPI-resistant HSV-1 mutant, that is markedly less virulent in vivo and slowly growing in tissue culture compared to the parental strain. Another BAY 57-1293-resistant UL5 mutant (Lys356Gln), which showed faster growth characteristics in cell culture, however, was at least equally virulent compared to the parent strain.
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Sequence Data
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-
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