Journal of Microbiology

Journal Articles

Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture: Hye Rim Hwang , Seok Cheon Kim , Se Hwan Kang , Chan Hee Lee; J. Microbiol. 2019;57(11):1033-1039. Published online October 28, 2019; DOI: https://doi.org/10.1007/s12275-019-9429-4

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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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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

Analysis of IE62 mutations found in Varicella-Zoster virus vaccine strains for transactivation activity: Hyemin Ko , Gwang Myeong Lee , Ok Sarah Shin , Moon Jung Song , Chan Hee Lee , Young Eui Kim , Jin-Hyun Ahn; J. Microbiol. 2018;56(6):441-448. Published online June 1, 2018; DOI: https://doi.org/10.1007/s12275-018-8144-x

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Abstract

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

Characterization and phylogenetic analysis of Varicella-zoster virus strains isolated from Korean patients: Min Ho Kim , Jeong Seon Jeon , In Kyo Kim , Ji Seon Park , Hosun Park , Ok Sarah Shin , Chan Hee Lee; J. Microbiol. 2017;55(8):665-672. Published online July 28, 2017; DOI: https://doi.org/10.1007/s12275-017-7171-3

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Abstract

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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Cross-reactive humoral immunity of clade 2 Oka and MAV/06 strain-based varicella vaccines against different clades of varicella–zoster virus
Ji-Young Hwang, Yunhwa Kim, Kyung-Min Lee, Ok Sarah Shin, Jeong-An Gim, Younchul Shin, Hosun Park
Human Vaccines & Immunotherapeutics.2023;[Epub] CrossRef
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

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