KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4

• DOI: 10.1016/j.celrep.2022.110788
• Publication Date: 2022-05-10T14:38:21Z
• Authors: Ashish Kumar; Yuanzhi Lyu; Yuichi Yanagihashi; Chanikarn Chantar...; Vladimir Majerciak; Michelle Salemi; Kang-Hsin Wang; Tomoki Inagaki; Frank Chuang; Ryan R. Davis; Clifford G. Tepper; Kazushi Nakano; Chie Izumiya; Michiko Shimoda; Ken-ichi Nakajima; Alexander Merleev; Zhi-Ming Zheng; Mel Campbell; Yoshihiro Izumiya
• Keywords: Lytic cycle; Kaposi's sarcoma-associated herpesvirus; Chromodomain; Virus latency

Kaposi sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and mechanisms underlying lytic reactivation unclear. Here, we study nuclear microenvironment of episomes show that latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. localize with CHD4 ADNP proteins, components cellular ChAHP complex. The proteins occupy 5′-region highly inducible lncRNAs terminal repeats genome together latency-associated antigen (LANA). Viral lncRNA competes binding, sequesters from genome, which also accompanied by detachment host chromosome docking sites. We propose model robust expression determines decision regulating LANA/CHD4 to episomes.