Primary infections with the varicella-zoster virus (VZV) result
in varicella, while latent reactivation leads to herpes zoster.
Both varicella and zoster can be prevented by live attenuated
vaccines. There have been reports suggesting that both clinical
VZV strains and those in vaccine preparations are genetically
polymorphic, containing mixtures of both wild-type
and vaccine-type sequences at certain vaccine-specific sites.
In this study, the genetic polymorphism of the VZV genome
was examined by analyzing the frequencies of minor alleles
at each nucleotide position. Next-generation sequencing of
the clinical VZV strain YC02 passaged in an in vitro cell culture
was used to identify genetically polymorphic sites (GPS),
where the minor allele frequency (MAF) exceeded 5%. The
number of GPS increased by 7.3-fold at high passages (p100)
when compared to low passages (p17), although the average
MAF remained similar. GPS were found in 6 open reading
frames (ORFs) in p17, 35, and 54 ORFs in p60 and p100, respectively.
GPS were found more frequently in the dispensable
gene group than the essential gene group, but the average MAF
was greater in the essential gene group. The most common
two major/minor base pairs were A/g and T/c. GPS were found
in all three passages at 16 positions, all located in the reiterated
(R) region. The population diversity as measured by Shannon
entropy increased in p60 and p100. However, the entropy
remained unchanged in the R regions.
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Genetic changes in plaque-purified varicella vaccine strain Suduvax during in vitro propagation in cell culture Hye Rim Hwang, Se Hwan Kang, Chan Hee Lee Journal of Microbiology.2021; 59(7): 702. CrossRef
Genetic diversity through social heterosis can increase virulence in RNA viral infections and cancer progression Saba Ebrahimi, Peter Nonacs Royal Society Open Science.2021;[Epub] CrossRef
Live attenuated vaccine strains have been developed for Varicella-
Zoster virus (VZV). Compared to clinically isolated
strains, the vaccine strains contain several non-synonymous
mutations in open reading frames (ORFs) 0, 6, 31, 39, 55, 62,
and 64. In particular, ORF62, encoding an immediate-early
(IE) 62 protein that acts as a transactivator for viral gene
expression, contains six non-synonymous mutations, but
whether these mutations affect transactivation activity of
IE62 is not understood. In this study, we investigated the
role of non-synonymous vaccine-type mutations (M99T,
S628G, R958G, V1197A, I1260V, and L1275S) of IE62 in
Suduvax, a vaccine strain isolated in Korea, for transactivation
activity. In reporter assays, Suduvax IE62 showed 2- to
4-fold lower transactivation activity toward ORF4, ORF28,
ORF29, and ORF68 promoters than wild-type IE62. Introduction
of individual M99T, S628G, R958G, or V1197A/
I1260V/L1275S mutations into wild-type IE62 did not affect
transactivation activity. However, the combination of M99T
within the N-terminal Sp transcription factor binding region
and V1197A/I1260V/L1275S within the C-terminal serineenriched
acidic domain (SEAD) significantly reduced the
transactivation activity of IE62. The M99T/V1197A/I1260V/
L1275S mutant IE62 did not show considerable alterations
in intracellular distribution and Sp3 binding compared to
wild-type IE62, suggesting that other alteration(s) may be
responsible for the reduced transactivation activity. Collectively,
our results suggest that acquisition of mutations in
both Met 99 and the SEAD of IE62 is responsible for the reduced
transactivation activity found in IE62 of the VZV
vaccine strains and contributes to attenuation of the virus.
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Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62 Ye Ji Kim, Doyeop Oh, Jaehoon Kim, Jeongtae Son, Jae Yun Moon, Ye Kyung Kim, Bin Ahn, Kyu Ri Kang, Daechan Park, Hyun Mi Kang Clinical Microbiology and Infection.2024; 30(11): 1466. CrossRef
Whole Transcriptome Analyses Reveal Differential mRNA and microRNA Expression Profiles in Primary Human Dermal Fibroblasts Infected with Clinical or Vaccine Strains of Varicella Zoster Virus Soo-Jin Oh, Sooyeon Lim, Moon Jung Song, Jin Hyun Ahn, Chan Hee Lee, Ok Sarah Shin Pathogens.2019; 8(4): 183. CrossRef
Varicella-zoster virus (VZV) is a causative agent of chickenpox
in primary infection and shingles after its reactivation
from latency. Complete or almost-complete genomic DNA
sequences for various VZV strains have been reported. Recently,
clinical VZV strains were isolated from Korean patients
whose genome was sequenced using high-throughput
sequencing technology. In this study, we analyzed single nucleotide
polymorphism (SNP) of VZV strains to genetically
characterize Korean clinical isolates. Phylogenetic analyses
revealed that three Korean strains, YC01, YC02, and YC03,
were linked to clade 2. Comprehensive SNP analysis identified
86 sites specific for the 5 VZV clades. VZV strains isolated
from Korea did not form a phylogenetic cluster. Rather,
YC02 and YC03 clustered strongly with Chinese strain 84-7
within clade 2, more specifically cluster 2a. Signature sequences
for the cluster 2a were identified and found to play an
important role in the separation of cluster 2a strains from
other clade 2 strains, as shown in substitution studies. Further
genetic analysis with additional strains isolated from Japan,
China, and other Asian countries would provide a novel insight
into the significance of two distinct subclades within
clade 2.
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Assessment of attenuation of varicella‐zoster virus vaccines based on genomic comparison Jae Yun Moon, Jina Seo, Jaewoo Lee, Daechan Park Journal of Medical Virology.2023;[Epub] CrossRef
Immunological characteristics of MAV/06 strain of varicella-zoster virus vaccine in an animal model Duckhyang Shin, Younchul Shin, Eunmi Kim, Hyojung Nam, Haiyan Nan, Jaewoo Lee BMC Immunology.2022;[Epub] CrossRef
Human herpesvirus diversity is altered in HLA class I binding peptides William H. Palmer, Marco Telford, Arcadi Navarro, Gabriel Santpere, Paul J. Norman Proceedings of the National Academy of Sciences.2022;[Epub] CrossRef
Genetic Change of Varicella-Zoster Virus Propagated in Cell Culture in Non-Natural Conditions Sang Hoon Yeon, Ji Seon Park, Se Hwan Kang, Chan Hee Lee Journal of Bacteriology and Virology.2021; 51(4): 178. CrossRef