Journal of Microbiology

Chan Hee Lee

8 Articles

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; J. Microbiol. 2021;59(7):702-707. Published online June 1, 2021; DOI: https://doi.org/10.1007/s12275-021-1062-3

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Abstract PDF: 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: 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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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

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 PDF

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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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
Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation
Ji-Soo Lim, Soo-Jin Oh, Ji-Yeun Hur, Subin Oh, Seuk-Min Ryu, Rafael T. Han, Hosun Park, Dawn M. E. Bowdish, Ok Sarah Shin
Journal of Biomedical Science.2026;[Epub] CrossRef
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 PDF

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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Microglial MARCO facilitates Varicella zoster virus uptake and triggers TLR2-mediated neuroinflammation
Ji-Soo Lim, Soo-Jin Oh, Ji-Yeun Hur, Subin Oh, Seuk-Min Ryu, Rafael T. Han, Hosun Park, Dawn M. E. Bowdish, Ok Sarah Shin
Journal of Biomedical Science.2026;[Epub] CrossRef
Varicella zoster virus mRNA vaccine candidate induced superior cellular immunity and comparable humoral and Fc-mediated immunity compared to the licensed subunit vaccine in a mouse model
Eun-Jeong Jang, Sivilay Xayaheuang, Ji-Young Hwang, Yunhwa Kim, Kyung-Min Lee, Seok-Tae Choi, Hye Won Kwak, Jae-Hwan Nam, Keunea Kim, Boomi Yoon, Jae Hyang Lim, Ho Seong Seo, Chang-Hoon Woo, Hosun Park
Human Vaccines & Immunotherapeutics.2025;[Epub] CrossRef
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

Requirement of the N-terminal residues of human cytomegalovirus UL112-113 proteins for viral growth and oriLyt-dependent DNA replication: Young-Eui Kim , Mi Young Park , Kyeong Jin Kang , Tae Hee Han , Chan Hee Lee , Jin-Hyun Ahn; J. Microbiol. 2015;53(8):561-569. Published online July 31, 2015; DOI: https://doi.org/10.1007/s12275-015-5301-3

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The UL112-113 region of the human cytomegalovirus (HCMV) genome encodes four phosphoproteins of 34, 43, 50, and 84 kDa that promote viral DNA replication. Co-transfection assays have demonstrated that self-interaction of these proteins via the shared N-termini is necessary for their intranuclear distribution as foci and for the efficient relocation of a viral DNA polymerase processivity factor (UL44) to the viral replication sites. However, the requirement of UL112- 113 N-terminal residues for viral growth and DNA replication has not been fully elucidated. Here, we investigated the effect of deletion of the N-terminal regions of UL112- 113 proteins on viral growth and oriLyt-dependent DNA replication. A deletion of the entire UL112 region or the region encoding the 25 N-terminal amino-acid residues from the HCMV (Towne strain) bacmid impaired viral growth in bacmid-transfected human fibroblast cells, indicating their requirement for viral growth. In co-immunoprecipitation assays using the genomic gene expressing the four UL112- 113 proteins together, the 25 N-terminal amino-acid residues were found to be necessary for stable expression of UL112- 113 proteins and their self-interaction. These residues were also required for efficient binding to and relocation of UL44, but not for interaction with IE2, an origin-binding transcription factor. In co-transfection/replication assays, replication of the oriLyt-containing plasmid was promoted by expression of intact UL112-113 proteins, but not by the expression of 25-amino-acid residue-deleted proteins. Our
results
demonstrate that the 25 N-terminal amino-acid residues of UL112-113 proteins that mediate self-interaction contribute to viral growth by promoting their binding to UL44 and the initiation of oriLyt-dependent DNA replication.

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Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review
Janine Zeng, Di Cao, Shaomin Yang, Dabbu Kumar Jaijyan, Xiaolian Liu, Songbin Wu, Ruth Cruz-Cosme, Qiyi Tang, Hua Zhu
Viruses.2023; 15(8): 1703. CrossRef
The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction
Declan L. Turner, Rommel A. Mathias
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Degradation of SAMHD1 Restriction Factor Through Cullin-Ring E3 Ligase Complexes During Human Cytomegalovirus Infection
Seokhwan Hyeon, Myoung Kyu Lee, Young-Eui Kim, Gwang Myeong Lee, Jin-Hyun Ahn
Frontiers in Cellular and Infection Microbiology.2020;[Epub] CrossRef
Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
Sangmin Kang, Jinjong Myoung
Journal of Microbiology.2017; 55(5): 319. CrossRef
Differential Requirement of Human Cytomegalovirus UL112-113 Protein Isoforms for Viral Replication
Tim Schommartz, Jiajia Tang, Rebekka Brost, Wolfram Brune, Klaus Frueh
Journal of Virology.2017;[Epub] CrossRef

Designing Primers from Multiple Sequences Using Matchup Program to Improve Detection of Hepatitis B Virus by Polymerase Chain Reaction: So Young Jang , Mi Suk Kim , Min Seok Park , Keon Myung Lee , Hwan Won Chung , Jongsik Chun , Chan Hee Lee; J. Microbiol. 2010;48(1):111-116. Published online March 11, 2010; DOI: https://doi.org/10.1007/s12275-009-0282-8

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Traditionally primers for PCR detection of viruses have been selected from genomic sequence of single or representative viral strain. However, high mutation rate of viral genomes often results in failure in detecting viruses in clinical and environmental samples. Thus, it seems necessary to consider primers designed from multiple viral sequences in order to improve detection of viral variants. Matchup is a program intended to select universal primers from multiple sequences. We designed using Matchup program primer pairs for HBV detection from 691 full genomic HBV DNA sequences available from NCBI GenBank database. Thousands of primer candidates were initially extracted and these were sequentially filtered down to 5 primer pairs. These primer pairs were tested by PCR using 5 HBV Korean HBsAg(+) patient sera, and eventually one universal primer pair was selected and named MUW (multiple-universal-worldwide). This primer pair, 3 HBV reference primer pairs reported by others and 1 commercial primer pair were compared using 86 HBV HBsAg(+) sera from Korean and Vietnamese patients. The detection rate for MUW primer pair was 72.1%, much greater than those obtained by reference and commercial primers (32.5 to 40.7%). The superiority of MUW primer pair appeared to be correlated with the conserved sequences of the forward primer binding sites and primer quality score. These results suggest that the universal primers designed by the Matchup program from multiple sequences could be useful in detecting viruses from clinical samples.

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Development of a new duplex real-time polymerase chain reaction assay for hepatitis B viral DNA detection
Shipeng Sun, Shuang Meng, Rui Zhang, Kuo Zhang, Lunan Wang, Jinming Li
Virology Journal.2011;[Epub] CrossRef

Analysis of Substitution Events in HIV-1 vif Gene of the Korean Clade: Chan Seung Park , Mi Sook Kim , Hyun Ah Yi , Dong Hun Lee , Keon Myung Lee , Chan Hee Lee; J. Microbiol. 2007;45(1):75-78.; DOI: https://doi.org/2487 [pii]

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Abstract PDF: Nucleotide and amino acid substitution pattern in vif gene of the Korean clade of HIV-1 isolated from Koreans were analyzed using consensus sequences. At nucleotide level, transition/transversion substitution ratio was 1.88, and nonsynonymous/synonymous substitution ratio was 2.67, suggesting a divergent <br>evolution in the Korean clade. At amino acid level, there were 17 substitutions and G→E substitution at position 37 may be responsible for change in predicted secondary structure.

Close Relationship Between SARS-Coronavirus and Group 2 Coronavirus: Ok Ju Kim , Dong Hun Lee , Chan Hee Lee; J. Microbiol. 2006;44(1):83-91.; DOI: https://doi.org/2332 [pii]

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Abstract PDF: The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV.

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