Journal of Microbiology

Jin-Hyun Ahn

3 Articles

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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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
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

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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Abstract PDF

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

Expression of Human Cytomegalovirus Immediate Early US3 Gene in Human Fibroblast Cells: Gyu-Cheol Lee , Chong-Kyo Lee , Jin-Hyun Ahn , Chan-Hee Lee; J. Microbiol. 2000;38(1):24-30.

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Abstract PDF: US3 gene is a member of the human cytomegalovirus (HCMV) immediate early gene. Although the precise functions of the US3 gene in HCMV replication and pathogenesis are not known, it has been reported to play a role in inhibiting major histocompatibility class I antigen presentation. For further knowledge of US3 gene expression, rabbit polyclonal antiserum of the US3 gene product was used for indirect immunofluorescence assay. In permissive human foreskin fibroblast (HFF) cells, US3 gene expression was detectable as crescent or half-moon shape in the perinuclear region at immediate early times after virus infection. HFF cells infected with mutant HCMV lacking US3 open reading frames were negative for US3 immunofluorescence assay. Double immunofluorescence assay using monoclonal antibody to gamma adaptin (specific for the Golgi complex) and rabbit anti-US3 antiserum revealed that US3 gene product could be localized to the Golgi complex. At later time after HCMV infection, US3 gene products were detected as globular aggregates in the cytosol. These aggregates were positive for gamma adaptin and stained with preimmune serum, suggesting a nonspecific reaction to the Golgi complex. Northern blot analysis revealed that transcription of US3 was observed only during immediate early times after virus infection (until 6 h postinfection). Therefore US3 gene expression appears to be confined to immediate early time and its gene products are localized to the Golgi complex as cres-cent shaped forms in the perinuclear cytoplasm.

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