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Basic Characteristics of Mutations
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Mutation Site
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K356N |
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Mutation Site Sentence
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Such mutations normally occur at a frequency of < or =10(-6)PFU. However, individual HSV-1 laboratory strains and some clinical isolates contained resistance mutations (e.g. UL5: Lys356Asn) at 10(-4)PFU. |
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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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HPI |
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Location
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- |
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Literature Information
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PMID
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20420855
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Title
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Effects of therapy using a helicase-primase inhibitor (HPI) in mice infected with deliberate mixtures of wild-type HSV-1 and an HPI-resistant UL5 mutant
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Author
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Sukla S,Biswas S,Birkmann A,Lischka P,Ruebsamen-Schaeff H,Zimmermann H,Field HJ
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Journal
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Antiviral research
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Journal Info
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2010 Jul;87(1):67-73
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Abstract
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Point mutations in the HSV-1 UL5 (helicase) gene confer resistance to helicase-primase inhibitors (HPIs), e.g. BAY 57-1293. Such mutations normally occur at a frequency of < or =10(-6)PFU. However, individual HSV-1 laboratory strains and some clinical isolates contained resistance mutations (e.g. UL5: Lys356Asn) at 10(-4)PFU. To address the possibility that pre-existing mutants at high frequency might have an impact on therapy using HPIs, deliberate mixtures were prepared to contain the SC16 UL5: Lys356Asn mutant in SC16 wild-type in the proportion of 1/500 or 1/50PFU. Mice were infected in the neck-skin with 5x10(4)PFU/mouse of wt alone, mutant alone, or the respective mixture. The mutant could not be detected in infectious virus yields from mice inoculated with the 1/500 mixture. However, resistant mutant was recovered from some treated mice inoculated with the 1/50 mixture. All mice inoculated with mixtures remained responsive to BAY 57-1293-therapy with no increase in clinical signs compared to treatment of wt-infected mice.
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Sequence Data
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-
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