Conserved herpesvirus kinases target the DNA damage response pathway and TIP60 histone acetyltransferase to promote virus replication |
| |
Authors: | Li Renfeng Zhu Jian Xie Zhi Liao Gangling Liu Jianyong Chen Mei-Ru Hu Shaohui Woodard Crystal Lin Jimmy Taverna Sean D Desai Prashant Ambinder Richard F Hayward Gary S Qian Jiang Zhu Heng Hayward S Diane |
| |
Institution: | Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA. |
| |
Abstract: | Herpesviruses, which are major human pathogens, establish life-long persistent infections. Although the α, β, and γ herpesviruses infect different tissues and cause distinct diseases, they each encode a conserved serine/threonine kinase that is critical for virus replication and spread. The extent of substrate conservation and the key common cell-signaling pathways targeted by these kinases are unknown. Using a human protein microarray high-throughput approach, we identify shared substrates of the conserved kinases from herpes simplex virus, human cytomegalovirus, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus. DNA damage response (DDR) proteins were statistically enriched, and the histone acetyltransferase TIP60, an upstream regulator of the DDR pathway, was required for efficient herpesvirus replication. During EBV replication, TIP60 activation by the BGLF4 kinase triggers EBV-induced DDR and also mediates induction of viral lytic gene expression. Identification of key cellular targets of the conserved herpesvirus kinases will facilitate the development of broadly effective antiviral strategies. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|