The relationship between histone modification and EBV reactivation

• Main Authors: Zhi-Ren Lu, 盧智仁
• Other Authors: Chi-Ju Chen
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/68928272436243771550

碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 98 === Epstein–Barr virus (EBV) is a ubiquitous human lymphotropic herpesvirus. EBV mainly infects B-lymphocytes and epithelial cells and is associated with several cancers. EBV life cycle include latent stage and lytic cycle. In latent stage, EBV genome is maintained as a chromosome-like episome. Previous lab study found that after viral reactivation, there were several histone modification changes on oriLyt, such as H3S10 phosphorylation and H3K9 acetylation. I want to figure out whether these modifications are important for viral reactivation and replication. At first, I focus on H3S10 phosphorylation and histone H3 acetylation. In the following experiments, I use inhibitors to inhibit the cellular enzymes that target H3S10 phosphorylation, dephosphorylation and histone H3 acetylation. Firstly, I use calyculin A to inhibit two of phosphatase, PP1 and PP2A in Akata cells. After using calyculin A to affect H3S10 dephosphorylation, I find that the viral reactivation is decresed after anti-hIgG induction. Secondly, to find out the role of viral reactivation of PP1 and PP2A, I choose okadaic acid to inhibit the only phosphatase, PP2A. I find that the viral reactivation is partially affected at low concentration, but the effect is similar to that of calyculin A at high concentration. Thirdly, I use H89 to target MSK1 and RSK2 that are H3S10 kinases. The result indicated that viral reactivation is also affected by H89 treatment. These results suggest that H3S10 phosphorylation might participate in viral reactivation process. Finally, I select curcumin to inhibit CBP activity, and observe the viral reactivation after using anti-hIgG to induction. I find that after curcumin treatment, the viral reactivation did not take place. I also find that all of these inhitors affect the Zta expression after anti-hIgG induction. I speculate that these histone modification enzymes might participate in viral reactivation process, and might play a part in Zp regulation.