Journal article
Varicella-Zoster Virus gE Escape Mutant VZV-MSP Exhibits an Accelerated Cell-to-Cell Spread Phenotype in both Infected Cell Cultures and SCID-hu Mice
Virology (New York, N.Y.), Vol.275(2), pp.306-317
09/30/2000
DOI: 10.1006/viro.2000.0507
PMID: 10998331
Abstract
Varicella-zoster virus is considered to have one of the most stable genomes of all human herpesviruses. In 1998, we reported the unanticipated discovery of a wild-type virus that had lost an immunodominant B-cell epitope on the gE ectodomain (VZV-MSP); the gE escape mutant virus exhibited an unusual pattern of egress. Further studies have now documented a markedly enhanced cell-to-cell spread by the mutant virus in cell culture. This property was investigated by laser scanning confocal microscopy combined with a software program that allows the measurement of pixel intensity of the fluorescent signal. For this new application of imaging technology, the VZV immediate early protein 62 (IE 62) was selected as the fluoresceinated marker. By 48 h postinfection, the number of IE 62-positive pixels in the VZV-MSP-infected culture was nearly fourfold greater than the number of pixels in a culture infected with a low-passage laboratory strain. Titrations by infectious center assays supported the above image analysis data. Confirmatory studies in the SCID-hu mouse documented that VZV-MSP spread more rapidly than other VZV strains in human fetal skin implants. Generally, the cytopathology and vesicle formation produced by other strains at 21 days postinfection were demonstrable with VZV-MSP at 14 days. To assess whether additional genes were contributing to the unusual VZV-MSP phenotype, ∼20 kb of the VZV-MSP genome was sequenced, including ORFs 31 (gB), 37 (gH), 47, 60 (gL), 61, 62 (IE 62), 66, 67 (gI), and 68 (gE). Except for a few polymorphisms, as well as the previously discovered mutation within gE, the nucleotide sequences within most open reading frames were identical to the prototype VZV-Dumas strain. In short, VZV-MSP represents a novel variant virus with a distinguishable phenotype demonstrable in both infected cell cultures and SCID-hu mice.
Details
- Title: Subtitle
- Varicella-Zoster Virus gE Escape Mutant VZV-MSP Exhibits an Accelerated Cell-to-Cell Spread Phenotype in both Infected Cell Cultures and SCID-hu Mice
- Creators
- Richard A Santos - Department of Microbiology, University of Iowa, Iowa City, Iowa, 52242Christopher C Hatfield - Department of Microbiology, University of Iowa, Iowa City, Iowa, 52242Nancy L Cole - Indiana University School of Medicine, SBCME, Notre Dame, Indiana, 46556Jorge A Padilla - Department of Microbiology, University of Iowa, Iowa City, Iowa, 52242Jennifer F Moffat - Department of Pediatrics, Stanford University School of Medicine, Stanford, California, 94305Ann M Arvin - Department of Pediatrics, Stanford University School of Medicine, Stanford, California, 94305William T Ruyechan - Department of Microbiology, State University of New York at Buffalo, Buffalo, New York, 14214John Hay - Department of Microbiology, State University of New York at Buffalo, Buffalo, New York, 14214Charles Grose - Department of Microbiology, University of Iowa, Iowa City, Iowa, 52242
- Resource Type
- Journal article
- Publication Details
- Virology (New York, N.Y.), Vol.275(2), pp.306-317
- DOI
- 10.1006/viro.2000.0507
- PMID
- 10998331
- NLM abbreviation
- Virology
- ISSN
- 0042-6822
- eISSN
- 1096-0341
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 09/30/2000
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093224202771
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