scholarly journals Characterization of Neutralizing Epitopes of Varicella-Zoster Virus Glycoprotein H

2008 ◽  
Vol 83 (4) ◽  
pp. 2020-2024 ◽  
Author(s):  
Yasushi Akahori ◽  
Kazuhiro Suzuki ◽  
Tohru Daikoku ◽  
Masae Iwai ◽  
Yoshihiro Yoshida ◽  
...  

ABSTRACT Varicella-zoster virus (VZV) glycoprotein H (gH) is the major neutralization target of VZV, and its neutralizing epitope is conformational. Ten neutralizing human monoclonal antibodies to gH were used to map the epitopes by immunohistochemical analysis and were categorized into seven epitope groups. The combinational neutralization efficacy of two epitope groups was not synergistic. Each epitope was partially or completely resistant to concanavalin A blocking of the glycomoiety of gH, and their antibodies inhibited the cell-to-cell spread of infection. The neutralization epitope comprised at least seven independent protein portions of gH that served as the target to inhibit cell-to-cell spread.

1996 ◽  
Vol 117 (1) ◽  
pp. 165-171 ◽  
Author(s):  
T. G. Wreghitt ◽  
J. Whipp ◽  
C. Redpath ◽  
W. Hollingworth

SummaryThis prospective study analyses infections with varicella-zoster virus (VZV) in Addenbrooke's Hospital, Cambridge during 1987–92 and examines the spread of infection. In total, 93 patients and staff experienced VZV infection. Twenty-one patients had varicella and 49 experienced zoster. None of 101 patients and 1 of 625 staff members in contact with varicella cases acquired infection. By contrast, 2 of 227 patients, and 5 of 1039 staff in contact with zoster cases acquired varicella. One out of 28 (3·6%) VZV antibody-negative patients and staff in contact with varicella acquired infection, compared with 5 out of 29 (17·2%) VZV antibody-negative patients and staff in contact with zoster. Thus, zoster was found to be a more frequent cause of nosocomial infection than varicella. Fourteen members of staff had VZV infection during the study period. One of 99 patients and none of 389 staff members in contact with these cases developed varicella. The cost of dealing with infection control for VZV infections in our hospital is estimated to be £714 per patient case and a total of £13204 per year.


1982 ◽  
Vol 73 (1) ◽  
pp. 383-386 ◽  
Author(s):  
Karen K. Biron ◽  
James A. Fyfe ◽  
Jean E. Noblin ◽  
Gertrude B. Elion

2011 ◽  
Vol 8 (1) ◽  
pp. 547 ◽  
Author(s):  
Jong Kim ◽  
Gyoo Jung ◽  
Yu Kim ◽  
Ga Ji ◽  
Hyung Kim ◽  
...  

2015 ◽  
Vol 135 (7) ◽  
pp. 1752-1762 ◽  
Author(s):  
Milica Vukmanovic-Stejic ◽  
Daisy Sandhu ◽  
Judith A. Seidel ◽  
Neil Patel ◽  
Toni O. Sobande ◽  
...  

2008 ◽  
Vol 83 (1) ◽  
pp. 228-240 ◽  
Author(s):  
Barbara Berarducci ◽  
Jaya Rajamani ◽  
Mike Reichelt ◽  
Marvin Sommer ◽  
Leigh Zerboni ◽  
...  

ABSTRACT Varicella-zoster virus (VZV) glycoprotein E (gE) is the most abundant glycoprotein in infected cells and, in contrast to those of other alphaherpesviruses, is essential for viral replication. The gE ectodomain contains a unique N-terminal region required for viral replication, cell-cell spread, and secondary envelopment; this region also binds to the insulin-degrading enzyme (IDE), a proposed VZV receptor. To identify new functional domains of the gE ectodomain, the effect of mutagenesis of the first cysteine-rich region of the gE ectodomain (amino acids 208 to 236) was assessed using VZV cosmids. Deletion of this region was compatible with VZV replication in vitro, but cell-cell spread of the rOka-ΔCys mutant was reduced significantly. Deletion of the cysteine-rich region abolished the binding of the mutant gE to gI but not to IDE. Preventing gE binding to gI altered the pattern of gE expression at the plasma membrane of infected cells and the posttranslational maturation of gI and its incorporation into viral particles. In contrast, deletion of the first cysteine-rich region did not affect viral entry into human tonsil T cells in vitro or into melanoma cells infected with cell-free VZV. These experiments demonstrate that gE/gI heterodimer formation is essential for efficient cell-cell spread and incorporation of gI into viral particles but that it is dispensable for infectious varicella-zoster virion formation and entry into target cells. Blocking gE binding to gI resulted in severe impairment of VZV infection of human skin xenografts in SCIDhu mice in vivo, documenting the importance of cell fusion mediated by this complex for VZV virulence in skin.


2004 ◽  
Vol 78 (13) ◽  
pp. 6799-6807 ◽  
Author(s):  
Charles Grose ◽  
Shaun Tyler ◽  
Geoff Peters ◽  
Joanne Hiebert ◽  
Gwen M. Stephens ◽  
...  

ABSTRACT Varicella-zoster virus (VZV) is considered to be one of the most genetically stable of all the herpesviruses. Yet two VZV strains with a D150N missense mutation within the gE glycoprotein were isolated in North America in 1998 and 2002. The mutant strains have an accelerated cell spread phenotype, which distinguishes them from all wild-type and laboratory viruses. Since the VZV genome contains 70 additional open reading frames (ORFs), the possibility existed that the phenotypic change was actually due to an as-yet-undiscovered mutation or deletion elsewhere in the genome. To exclude this hypothesis, the entire genomes of the two mutant viruses were sequenced and found to contain 124,883 (VZV-MSP) and 125,459 (VZV-BC) nucleotides. Coding single-nucleotide polymorphisms (SNPs) were identified in 14 ORFs. One missense mutation was discovered in gH, but none was found in gB, gI, gL, or gK. There were no coding SNPs in the major regulatory protein ORF 62. One polymorphism was discovered which could never have been anticipated based on current knowledge of herpesvirus genomics, namely, the origins of replication differed from those in the prototype strain but not in a manner expected to affect cell spread. When the two complete mutant VZV sequences were surveyed in their entirety, the most reasonable conclusion was that the increased cell spread phenotype was dependent substantially or solely on the single D150N polymorphism in glycoprotein gE. The genomic results also expanded the evolutionary database by identifying which VZV ORFs were more likely to mutate over time.


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