- Genetic changes in plaque-purified varicella vaccine strain Suduvax during in vitro propagation in cell culture
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Hye Rim Hwang , Se Hwan Kang , Chan Hee Lee
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J. Microbiol. 2021;59(7):702-707. Published online June 1, 2021
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DOI: https://doi.org/10.1007/s12275-021-1062-3
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 Abstract
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Infection by varicella-zoster virus (VZV) can be prevented by
using live attenuated vaccines. VZV vaccine strains are known
to evolve rapidly in vivo, however, their genetic and biological
effects are not known. In this study, the plaque-purified vaccine
strain Suduvax (PPS) was used to understand the genetic
changes that occur during the process of propagation in in
vitro cell culture. Full genome sequences of three different passages
(p4, p30, and p60) of PPS were determined and compared
for genetic changes. Mutations were found at 59 positions.
The number of genetically polymorphic sites (GPS) and
the average of minor allele frequency (MAF) at GPSs were not
significantly altered after passaging in cell culture up to p60.
The number of variant nucleotide positions (VNPs), wherein
GPS was found in at least one passage of PPS, was 149. Overall,
MAF changed by less than 5% at 52 VNPs, increased by more
than 5% at 42 VNPs, and decreased by more than 5% at 55
VNPs in p60, compared with that seen in p4. More complicated
patterns of changes in MAF were observed when genetic
polymorphism at 149 VNPs was analyzed among the three
passages. However, MAF decreased and mixed genotypes became
unequivocally fixed to vaccine type in 23 vaccine-specific
positions in higher passages of PPS. Plaque-purified Suduvax
appeared to adapt to better replication during in vitro cell
culture. Further studies with other vaccine strains and in vivo
studies will help to understand the evolution of the VZV vaccine.
- Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture
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Hye Rim Hwang , Seok Cheon Kim , Se Hwan Kang , Chan Hee Lee
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J. Microbiol. 2019;57(11):1033-1039. Published online October 28, 2019
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DOI: https://doi.org/10.1007/s12275-019-9429-4
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Abstract
PDF
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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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Citations
Citations to this article as recorded by  - Genomic comparison reveals single-nucleotide polymorphic sites and attenuation-associated site combinations specific to Chinese live attenuated varicella-zoster virus vaccines
Yuchan Zhang, Xuhua Duan, Yuanyuan Cai, Mingren Wang, Ziqiang Wang, Minghui Song, Tianyi Qiu, Xuanyi Wang, Hong Shao
Human Vaccines & Immunotherapeutics.2026;[Epub] CrossRef -
Biological relevance of
in vitro
cellular models to study varicella-zoster virus—host cell interactome: current limitations and future perspectives
Jonas Govaerts, Charlotte Goethals, Elise Van Breedam, Catherine Sadzot-Delvaux, Peter Delputte, Benson Ogunjimi, Marielle Lebrun, Peter Ponsaerts, Stanley Perlman
Microbiology and Molecular Biology Reviews.2025;[Epub] CrossRef - 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
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