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Basic Characteristics of Mutations
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Mutation Site
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L393P |
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Mutation Site Sentence
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The KOS-NA mutant of HSV-1 KOS [25] contains non-synonymous mutations in the UL39 gene, resulting in L393P and R950H substitutions in ICP6, as well as three additional mutations in US7 and RS1 [24]. |
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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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ICP6 |
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Standardized Encoding Gene
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UL39
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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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- |
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Location
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USA |
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Literature Information
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PMID
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35632611
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Title
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Efficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication
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Author
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Wang H,Davido DJ,Mostafa HH,Morrison LA
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Journal
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Viruses
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Journal Info
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2022 Apr 22;14(5):869
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Abstract
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We previously isolated an HSV-1 mutant, KOS-NA, that contains two non-synonymous mutations in UL39. One of the mutations, resulting in an R950H amino acid substitution in ICP6, renders KOS-NA severely neuro-attenuated and significantly reduces HSV-1 latency. Vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated eye diseases even at a very low immunizing dose, indicating its utility as a vaccine scaffold. Because KOS-NA contains a neuro-attenuating mutation in a single gene, we sought to improve its safety by deleting a portion of the UL29 gene whose protein product, ICP8, is essential for viral DNA replication. Whereas KOS-NA reduced replication of HSV-1 challenge virus in the corneal epithelium and protected mice against blepharitis and keratitis induced by the challenge virus, KOS-NA/8- and an ICP8- virus were significantly less efficacious except at higher doses. Our results suggest that the capacity to replicate, even at significantly reduced levels compared with wild-type HSV-1, may be an important feature of an effective vaccine. Means to improve safety of attenuated viruses as vaccines without compromising efficacy should be sought.
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Sequence Data
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-
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