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- 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
- Heightened incidence of adverse events associated with a live attenuated varicella vaccine strain that lacks critical genetic polymorphisms in open reading frame 62
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