Vaccine-type mutations identified in Varicella zoster virus passaged in cell culture

Kim, Seok Cheon; Won, Youn Hee; Park, Ji Seon; Jeon, Jeong Seon; Ahn, Jinhee; Song, Mee Hyun; Shin, Ok Sarah; Lee, Chan Hee

doi:10.1016/j.virusres.2017.12.004

Cited by 5 publications

(7 citation statements)

References 26 publications

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“…To date, limited data has been published regarding the Korean vaccine strain SuduVax [10,11,31]. The comparative genome sequencing of clinical and vaccine strains of VZV revealed 24 vaccine-specific SNP sites that we previously detected in high passage clinical strains, such as Ellen, 32p72, YC01, and YC02 [20]. In particular, YC01-high (passage number 110) had seven SNPs, with five SNPs in ORF62.…”

Section: Discussionmentioning

confidence: 87%

“…We previously reported vaccine-type mutations associated with extensive in vitro serial passaging in VZV clinical strains, and there were seven vaccine-associated SNPs accumulated in highly passaged YC01 strains [12,20]. Interestingly, almost 40% of vaccine-type mutations were detected in ORF62, indicating that functional alterations of ORF62 caused by these mutations may be essential for viral attenuation.…”

Section: Discussionmentioning

confidence: 99%

“…KJ808816) has been described previously [21] and was propagated in MRC-5 cells. YC01 low passage (YC01-low) and high passage (YC01-high) virus preparation was described in our previous study [20]. SuduVax was sequenced and characterized as described previously [10].…”

Section: Cells and Virusesmentioning

confidence: 99%

“…In this study, we used RNA-seq and small RNA-seq to comprehensively analyze whole transcriptomes following wildtype (YC01 low passage) and attenuated (YC01 high passage, SuduVax cell-associated (CA) or cell-free (CF) preparation, and VarilRix) VZV infection. The YC01 strain was isolated from a zoster patient in Korea, whereas vaccine-type mutations were found in highly passaged YC01 strains [20]. Our work provides a global overview of virus type-specific mRNA and miRNA profiles, and gives an insight into the effect of vaccine-type VZV mutations on host immune signaling and the microRNA network.…”

Section: Introductionmentioning

confidence: 96%

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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

Lim

Song

et al. 2019

Pathogens

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Licensed live attenuated vaccines have been developed to prevent varicella zoster virus (VZV) infection, which causes chickenpox and shingles. The genomic sequences of both clinical- and vaccine-derived VZV strains have been analyzed previously. To further characterize the molecular signatures and complexity of wildtype (clinical) versus attenuated (vaccine-derived) VZV-mediated host cellular responses, we performed high-throughput next generation sequencing to quantify and compare the expression patterns of mRNAs and microRNAs (miRNAs) in primary human dermal fibroblasts (HDFs) infected with wildtype (YC01 low passage) and attenuated (YC01 high passage, SuduVax, and VarilRix) VZV strains. 3D-multidimensional scaling of the differentially expressed genes demonstrated the distinct grouping of wildtype and attenuated strains. In particular, we observed that HDFs infected with attenuated strains had more differentially expressed genes (DEGs) involved in the retinoic-acid inducible gene–I-like receptor and interferon-mediated signaling pathways compared with wildtype strains. Additionally, miRNA expression patterns were profiled following the infection of HDFs with VZV. Small RNA sequencing identified that several miRNAs were upregulated, including miR-146a-5p, which has been associated with other herpesvirus infections, whereas let-7a-3p was downregulated in both wildtype and attenuated VZV-infected cells. This study identified genes and miRNAs that may be essential in VZV pathogenesis.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Cells and Virusesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 2 more Smart Citations

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

Lim

Song

et al. 2019

Pathogens

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“…The T to C mutation at position 106262 was observed in p60 (34) and p60 (34->37), thus it could be considered to be a low temperature-specific mutation. However, same T to C mutation at this position occurred even when YC02 and another clinical strain, YC01, were cultured up to p110 in natural culture conditions (24). Therefore, it is controversial whether the T to C mutation at position 106262 is a low temperature-specific mutation.…”

Section: Discussionmentioning

confidence: 99%

Genetic Change of Varicella-Zoster Virus Propagated in Cell Culture in Non-Natural Conditions

Yeon¹,

Park²,

Kang³

et al. 2021

J Bacteriol Virol.

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Primary infection of varicella-zoster virus (VZV) causes varicella and often leads to zoster after reactivation from latency. Both varicella and zoster can be prevented by live attenuated vaccines, but the molecular mechanism of attenuation is not clearly understood. In this study, it was attempted to understand mechanism of attenuating mutation in VZV by in vitro propagation in non-natural conditions such as low temperature or non-human cell. Clinical strain YC02 was subcultured in vitro up to 60 times. Comparison of the genome sequences of YC02 variants cultured under various conditions identified specific mutations occurred in non-natural conditions. The mutations specific for low temperature culture and non-human cell culture were identified in 8 and 2 positions, respectively. Two vaccine-specific mutations in position 97748 and 106262 were identified during subculture in non-natural conditions. Genetic diversity as measured by genetic polymorphism and Shannon entropy decreased when cultured in guinea pig lung cell culture. The infectivity of YC02 cultured at low temperature appeared similar to that cultured in natural condition. On the other hands, infectivity decreased significantly when YC02 was subcultured in non-human cell. Further studies on mutations and genetic diversity of clinical strain cultured in non-natural conditions will help to elucidate the molecular mechanism of VZV attenuation.

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Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture

et al. 2019

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Vaccine-type mutations identified in Varicella zoster virus passaged in cell culture

Cited by 5 publications

References 26 publications

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

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

Genetic Change of Varicella-Zoster Virus Propagated in Cell Culture in Non-Natural Conditions

Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture

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