| Title | Analysis of IE62 mutations found in Varicella-Zoster virus vaccine strains for transactivation activity |
|---|---|
| Author | Hyemin Ko1, Gwang Myeong Lee1, Ok Sarah Shin2, Moon Jung Song3, Chan Hee Lee4, Young Eui Kim1, and Jin-Hyun Ahn1* |
| Address | 1Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Suwon 16419, Republic of Korea, 2Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 08308, Republic of Korea, 3Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea, 4Department of Microbiology, Chungbuk National University, Cheongju 28644, Republic of Korea |
| Bibliography | Journal of Microbiology, 56(6),441–448, 2018, |
| DOI | 10.1007/s12275-018-8144-x |
| Key Words | Varicella-Zoster virus, vaccine, IE62, mutation, Suduvax |
| 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. |