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Text
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Pages
3843–3853
Issue
5
Volume
73
Dublin Core
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Title
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Intrastrain variants of herpes simplex virus type 1 isolated from a neonate with fatal disseminated infection differ in the ICP34.5 gene, glycoprotein processing, and neuroinvasiveness.
Publisher
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Journal of virology
Date
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1999
1999-05
Subject
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Humans; Male; Animals; Mice; Amino Acid Sequence; *Genetic Variation; Base Sequence; Molecular Sequence Data; Polymerase Chain Reaction/methods; DNA; Deoxyribonuclease BamHI; Deoxyribonuclease EcoRI; Glycoproteins/metabolism; Viral Envelope Proteins/analysis; Viral Proteins/*genetics; Genes; Viral; Animal; Disease Models; Herpesvirus 1; Inbred BALB C; Amino Acid; Sequence Homology; Sequence Analysis; Nucleic Acid; Polymorphism; *Protein Processing; Post-Translational; Human/*genetics/growth & development/isolation & purification; Restriction Fragment Length
Creator
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Bower J R; Mao H; Durishin C; Rozenbom E; Detwiler M; Rempinski D; Karban T L; Rosenthal K S
Description
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Two intrastrain variants of herpes simplex virus type 1 (HSV-1) were isolated from a newborn with fatal disseminated infection. A small-plaque-producing variant (SP7) was the predominant virus (\textgreater99%) in the brain, and a large-plaque-producing variant (LP5) was the predominant virus (\textgreater99%) in the lung and gastrointestinal tract. EcoRI and BamHI restriction fragment patterns indicated that SP7 and LP5 are related strains. The large-plaque variants produced plaques similar in size to those produced by HSV-1 KOS. Unlike LP5 or KOS, SP7 was highly cell associated and processing of glycoprotein C and glycoprotein D was limited to precursor forms in infected Vero cells. The large-plaque phenotype from KOS could be transferred into SP7 by cotransfection of plasmids containing the EK or JK EcoRI fragment or a 3-kb plasmid with the UL34.5 gene of HSV-1 KOS together with SP7 DNA. PCR analysis using primers from within the ICP34.5 gene indicated differences for SP7, LP5, and KOS. Sequencing data indicated two sets of deletions in the UL34.5 gene that distinguish SP7 from LP5. Both SP7 and LP5 variants were neurovirulent (lethal following intracranial inoculation of young BALB/c mice); however, the LP5 variant was much less able to cause lethal neuroinvasive disease (footpad inoculation) whereas KOS caused no disease. Passage of SP7 selected for viruses (SLP-5 and SLP-10) which were attenuated for lethal neuroinvasive disease, were not cell-associated, and differed in the UL34.5 gene. UL34.5 from SLP-5 or SLP-10 resembled that of KOS. These findings support a role for UL34.5 in promoting virus egress and for neuroinvasive disease.
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Genetic Variation
*Protein Processing
1999
Amino Acid
Amino Acid Sequence
Animal
Animals
Base Sequence
Bower J R
Deoxyribonuclease BamHI
Deoxyribonuclease EcoRI
Detwiler M
Disease Models
DNA
Durishin C
Genes
Glycoproteins/metabolism
Herpesvirus 1
Human/*genetics/growth & development/isolation & purification
Humans
Inbred BALB C
Journal of virology
Karban T L
Male
Mao H
Mice
Molecular Sequence Data
Nucleic Acid
Polymerase Chain Reaction/methods
Polymorphism
Post-Translational
Rempinski D
Restriction Fragment Length
Rosenthal K S
Rozenbom E
Sequence Analysis
Sequence Homology
Viral
Viral Envelope Proteins/analysis
Viral Proteins/*genetics