Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency (Nat Med, 2009, 15:1312-1317)

報告日期: 2010/04/20
報告時間: 17:10/18:00
報告學生: 賴曉菁(英文報告)
講評老師: 陳舜華
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990420-3.pdf

Inhibition of histone demethylase LSD1 blocks a-herpesvirus lytic replication and reactivation from latency

 

Speaker: Hsiao-Ching Lai

Commentator: Dr. Shun-Hua Chen

Date: 2010.4.20

Room: 602

 

Abstract:

    Herpes simplex virus 1 (HSV-1) and varicella zoster virus are a-herpesviruses which can establish life-long latency in human neurons with no virion production. Reactivation from latency results in viral lytic replication and causes severe disorders such as herpes simplex encephalitis or herpes zoster. Thus, inhibition of the viral reactivation and lytic replication may reduce the morbidity and mortality of herpesvirus infection. An important factor for controlling a-herpesvirus lytic infection is chromatin modification of the viral genome. During herpesvirus reactivation, methyltransferase complexes are recruited to viral lytic promoters by a human transcriptional activator host cell factor-1 (HCF-1), leading to methylation at histone H3 lysine 4 and promoting viral gene transcription. In this study, the authors found that HCF-1 also recruits the lysine-specific demethylase-1 (LSD1) to remove suppressive methylation from histone H3 lysine 9 (H3K9) on viral lytic promoters. Knockdown of LSD1 or treatment with its inhibitors increases the H3K9 methylation and suppresses viral lytic gene expression and virion production. Inhibition of LSD1 also blocks reactivation of HSV-1. This finding provides insight that viral chromatin modification can be affected by pharmaceutical inhibitors and serves as a target for controlling replication and reactivation of a-herpesviruses.

 

References:

1. Knipe, D.M., and Cliffe, A. (2008). Chromatin control of herpes simplex virus lytic and latent infection. Nat Rev Microbiol 6, 211-221.

2. Liang, Y., Vogel, J.L., Narayanan, A., Peng, H., and Kristie, T.M. (2009). Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency. Nat Med 15, 1312-1317.

3. Steiner, I., Kennedy, P.G., and Pachner, A.R. (2007). The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 6, 1015-1028.