Distribution of varicella-zoster virus (VZV) wild-type genotypes in northern and southern Europe: Evidence for high conservation of circulating genotypes

Varicella-zoster virus vaccination is recommended for virtually all young children in the United States, Canada, and several other countries. Varicella vaccine is a live attenuated virus that retains some of its neurotropic properties. Herpes zoster caused by vaccine virus still occurs in immunized children, although the rate is much lower than in children who had wild-type varicella. It was commonly thought that 2 varicella vaccinations would protect children against the most serious complication of meningitis following herpes zoster; however, 2 meningitis cases have already been published. We now report a third case of varicella vaccine meningitis and define risk factors shared by all 3 immunized adolescents. The diagnosis in cerebrospinal fluid in this third case was verified by amplifying and sequencing portions of the viral genome, to document fixed alleles found only in the vaccine strain. Viral antibody was also detected in the cerebrospinal fluid by confocal microscopy. When compared with the other 2 cases, remarkably all 3 were 14 years old when meningitis occurred. All 3 were treated with intravenous acyclovir, with complete recovery. The adolescent in our case report also had recurrent asthma, which was treated with both prednisone tablets and beclomethasone inhaler before onset of meningitis. When the 3 cases were considered together, they suggested that immunity to varicella-zoster virus may be waning sufficiently in some twice-immunized adolescents to make them vulnerable to varicella vaccine virus reactivation and subsequent meningitis. This complication rarely happens in children after wild-type varicella.

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Genotypes of varicella-zoster virus wild-type strains in Germany

Journal of Medical Virology ◽

10.1002/jmv.21178 ◽

2008 ◽

Vol 80 (6) ◽

pp. 1123-1130 ◽

Cited By ~ 21

Author(s):

A. Sauerbrei ◽

R. Zell ◽

A. Philipps ◽

P. Wutzler

Keyword(s):

Varicella Zoster Virus ◽

Wild Type ◽

Varicella Zoster ◽

Type Strains

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Genotypic Analysis of Varicella-Zoster Virus and Its Seroprevalence in Finland

Clinical and Vaccine Immunology ◽

10.1128/cvi.00348-06 ◽

2007 ◽

Vol 14 (9) ◽

pp. 1057-1061 ◽

Cited By ~ 13

Author(s):

Marjaleena Koskiniemi ◽

Maija Lappalainen ◽

D. Scott Schmid ◽

Elena Rubtcova ◽

Vladimir N. Loparev

Keyword(s):

Varicella Zoster Virus ◽

Immunoglobulin G ◽

Pediatric Patients ◽

Age Groups ◽

Wild Type ◽

Finnish Population ◽

Serum Samples ◽

Varicella Zoster ◽

Genotypic Analysis ◽

Specific Immunoglobulin

ABSTRACT We evaluated the seroprevalence of varicella-zoster virus (VZV) in the Finnish population among various age groups and genetically characterized VZV strains from documented cases of varicella and zoster. VZV-specific immunoglobulin G was measured in 2,842 serum samples that had been submitted for virological studies to the Department of Virology, University of Helsinki, from 1995 to 1996. Specimens for VZV genotyping were obtained from vesicular lesions from two pediatric patients and 26 adult patients. Seroprevalence to VZV varied markedly by age: 45% in children aged ≤2 months, 12.5% in children aged 6 to 8 months, and >90% in children near 10 years of age, plateauing thereafter into advanced age. The seroprevalence rates indicate that in Finland, as in other countries with temperate climates, primary VZV infection usually occurs during the first decade of life. Twenty-eight VZV DNA-positive specimens were analyzed to identify VZV vaccine and wild-type genotypes. All analyzed specimens were wild type and the European (E) genotype.

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Variability of Immediate-Early Gene 62 in German Varicella-Zoster Virus Wild-Type Strains

Journal of Clinical Microbiology ◽

10.1128/jcm.01550-09 ◽

2009 ◽

Vol 47 (11) ◽

pp. 3717-3720 ◽

Cited By ~ 1

Author(s):

A. Sauerbrei ◽

K. Bohn ◽

R. Zell ◽

P. Wutzler

Keyword(s):

Varicella Zoster Virus ◽

Immediate Early Gene ◽

Early Gene ◽

Immediate Early ◽

Wild Type ◽

Varicella Zoster ◽

Type Strains

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Differentiation between wild-type and vaccines strains of varicella zoster virus (VZV) based on four single nucleotide polymorphisms

Epidemiology and Infection ◽

10.1017/s0950268817001509 ◽

2017 ◽

Vol 145 (12) ◽

pp. 2618-2625

Author(s):

L. JIN ◽

S. XU ◽

P. A. C. MAPLE ◽

W. XU ◽

K. E. BROWN

Keyword(s):

Single Nucleotide Polymorphisms ◽

Varicella Zoster Virus ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Chain Reactions ◽

Varicella Zoster ◽

Polymerase Chain Reactions ◽

Set Up ◽

The Uk

SummaryVaricella–zoster virus (VZV) infection (chickenpox) results in latency and subsequent reactivation manifests as shingles. Effective attenuated vaccines (vOka) are available for prevention of both illnesses. In this study, an amplicon-based sequencing method capable of differentiating between VZV wild-type (wt) strains and vOka vaccine is described. A total of 44 vesicular fluid specimens collected from 43 patients (16 from China and 27 from the UK) with either chickenpox or shingles were investigated, of which 10 had received previous vaccination. Four sets of polymerase chain reactions were set up simultaneously with primers amplifying regions encompassing four single nucleotide polymorphisms (SNPs), ‘69349-106262-107252-108111’. Nucleotide sequences were generated by Sanger sequencing. All samples except one had a wt SNP profile of ‘A-T-T-T’. The sample collected from a patient who received vaccine 7–10 days ago, along with VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile ‘G-C-C-C’. The results show that this method can distinguish vaccine-derived virus from wt viruses from main four clades, (clades 1–4) and should be of utility worldwide.

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Restriction fragment differences between the genomes of the Oka varicella vaccine virus and american wild-type varicella-zoster virus

Journal of Medical Virology ◽

10.1002/jmv.1890290108 ◽

1989 ◽

Vol 29 (1) ◽

pp. 38-45 ◽

Cited By ~ 15

Author(s):

Susan G. Adams ◽

Dennis E. Dohner ◽

Lawrence D. Gelb

Keyword(s):

Varicella Zoster Virus ◽

Restriction Fragment ◽

Varicella Vaccine ◽

Vaccine Virus ◽

Wild Type ◽

Varicella Zoster

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Drug Resistance of Clinical Varicella-Zoster Virus Strains Confirmed by Recombinant Thymidine Kinase Expression and by Targeted Resistance Mutagenesis of a Cloned Wild-Type Isolate

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05115-14 ◽

2015 ◽

Vol 59 (5) ◽

pp. 2726-2734 ◽

Cited By ~ 15

Author(s):

Anne-Kathrin Brunnemann ◽

Kathrin Bohn-Wippert ◽

Roland Zell ◽

Andreas Henke ◽

Martin Walther ◽

...

Keyword(s):

Amino Acid ◽

Varicella Zoster Virus ◽

Thymidine Kinase ◽

Fluorescent Protein ◽

Phenotypic Characterization ◽

Antiviral Resistance ◽

Amino Acid Substitutions ◽

Wild Type ◽

Varicella Zoster ◽

Virus Strains

ABSTRACTIn this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method ofen passantmutagenesis was used. Targeted mutations within ORF36 and/or ORF28 and an autonomously expressed gene of the monomeric red fluorescent protein for plaque identification were introduced into the European wild-type VZV strain HJO. Plaque reduction assays revealed that the amino acid substitutions with unknown functions in TK, Q303stop, N334stop, A163stop, and the deletion of amino acids 7 to 74 aa (Δaa 7 to 74), were associated with resistance against acyclovir (ACV), penciclovir, or brivudine, whereas the L73I substitution and the Pol substitutions T237K and A955T revealed sensitive viral phenotypes. The results were confirmed by quantitative PCR by measuring the viral load under increasing ACV concentrations. In conclusion, analyzing the enzymatic activities of recombinant TK proteins represent a useful tool for evaluating the significance of amino acid substitutions in the antiviral resistance of clinical VZV strains. However, direct testing of replication-competent viruses by the introduction of nonsynonymous mutations in a VZV bacterial artificial chromosome usingen passantmutagenesis led to reliable phenotypic characterization results.

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