Human cytomegalovirus exploits host chromatin remodeler MORC2 to promote the DNA damage response on viral genomes
4 affiliations
- 1Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.
- 2School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
- 3The Research Institute of Basic Sciences, Seoul National University, Seoul, Republic of Korea.
- 4SNU Institute for Virus Research, Seoul National University, Seoul, Republic of Korea.
Abstract
Human cytomegalovirus (HCMV) harbors a 230-kb double-stranded DNA genome whose replication induces extensive DNA damage during lytic infection. Because HCMV lacks canonical DNA repair machinery, it relies on host DNA damage response (DDR) pathways. However, the mechanisms that govern the preferential recruitment and function of host DDR proteins on viral genomes remain poorly understood. Here, we show that HCMV co-opts the host chromatin remodeler MORC Family CW-type zinc finger 2 (MORC2) to promote DDR activation on viral genomes. HCMV infection induces MORC2 expression, which is important for efficient viral DNA replication and progeny virus production. We found that MORC2 redistributes to viral replication compartments (vRCs) in HCMV-infected cells and enhances viral chromatin accessibility in an ATPase-dependent manner, thereby facilitating γH2AX accumulation and the recruitment of DNA repair factors to vRCs. Furthermore, we found that HCMV UL112-113-mediated phase separation facilitates MORC2 recruitment to vRCs, promoting efficient DDR signaling on viral genomes. Together, these findings provide a mechanistic framework for how DNA viruses alleviate replication stress by hijacking host chromatin remodelers. Author summary: DNA viruses depend on host DNA damage response (DDR) to preserve genome integrity during replication, but the mechanisms underlying preferential recruitment of DDR machinery to viral genomes are poorly understood. We show that human cytomegalovirus (HCMV) co-opts the host chromatin remodeler MORC2 to promote viral chromatin accessibility, DDR activation, and subsequent repair factor accumulation on viral genomes. UL112–113-mediated phase separation promotes MORC2 recruitment into replication compartments, thereby facilitating DDR activation on viral genomes. These findings reveal a mechanism by which a DNA virus hijacks host genome maintenance functions on its own DNA and identify MORC2 as a key host factor supporting HCMV replication.
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BibTeX
@article{jeong2026human,
title = {{Human cytomegalovirus exploits host chromatin remodeler MORC2 to promote the DNA damage response on viral genomes}},
author = {Jiseok Jeong and Dongjoon Jeong and Sungwon Lee and Junhyun Park and Hyewon Kim and Kwangseog Ahn},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014693},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014693},
note = {CC BY},
}
RIS
TY - JOUR
TI - Human cytomegalovirus exploits host chromatin remodeler MORC2 to promote the DNA damage response on viral genomes
AU - Jiseok Jeong
AU - Dongjoon Jeong
AU - Sungwon Lee
AU - Junhyun Park
AU - Hyewon Kim
AU - Kwangseog Ahn
PY - 2026
DA - 2026/10/14
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014693
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014693
AB - Human cytomegalovirus (HCMV) harbors a 230-kb double-stranded DNA genome whose replication induces extensive DNA damage during lytic infection. Because HCMV lacks canonical DNA repair machinery, it relies on host DNA damage response (DDR) pathways. However, the mechanisms that govern the preferential recruitment and function of host DDR proteins on viral genomes remain poorly understood. Here, we show that HCMV co-opts the host chromatin remodeler MORC Family CW-type zinc finger 2 (MORC2) to promote DDR activation on viral genomes. HCMV infection induces MORC2 expression, which is important for efficient viral DNA replication and progeny virus production. We found that MORC2 redistributes to viral replication compartments (vRCs) in HCMV-infected cells and enhances viral chromatin accessibility in an ATPase-dependent manner, thereby facilitating γH2AX accumulation and the recruitment of DNA repair factors to vRCs. Furthermore, we found that HCMV UL112-113-mediated phase separation facilitates MORC2 recruitment to vRCs, promoting efficient DDR signaling on viral genomes. Together, these findings provide a mechanistic framework for how DNA viruses alleviate replication stress by hijacking host chromatin remodelers. Author summary: DNA viruses depend on host DNA damage response (DDR) to preserve genome integrity during replication, but the mechanisms underlying preferential recruitment of DDR machinery to viral genomes are poorly understood. We show that human cytomegalovirus (HCMV) co-opts the host chromatin remodeler MORC2 to promote viral chromatin accessibility, DDR activation, and subsequent repair factor accumulation on viral genomes. UL112–113-mediated phase separation promotes MORC2 recruitment into replication compartments, thereby facilitating DDR activation on viral genomes. These findings reveal a mechanism by which a DNA virus hijacks host genome maintenance functions on its own DNA and identify MORC2 as a key host factor supporting HCMV replication.
SN - 1553-7374
SN - 1553-7366
ER -