ICP22-defined condensates mediate RNAPII deubiquitylation by UL36 and promote HSV-1 transcription
Herpes simplex virus type I (HSV-1) infection leads to RNA polymerase II (RNAPII) degradation and host transcription shutdown. We show that ICP22 defines the virus-induced chaperone-enriched (VICE) domain through liquid-liquid phase separation. Condensate-disrupting point mutations of ICP22 increase ubiquitin modification of RNAPII Ser-2P; reduce its level and occupancy on viral genes; impair viral gene expression, particularly late genes; and severely reduce viral titers. When proteasome activity is blocked, ubiquitinated RNAPII Ser-2P and the viral UL36 begin to accumulate in the ICP22 condensates. The ubiquitin-specific protease (USP) deubiquitinase domain of UL36 interacts with and erases ubiquitin modification from RNAPII Ser-2P, protecting it from degradation in infected cells. A virus carrying a catalytic mutant of the UL36 USP diminishes cellular RNAPII Ser-2P levels, viral transcription, and growth. Thus, ICP22 condensates are processing centers where RNAPII Ser-2P is recruited to be deubiquitinated to ensure viral transcription when host transcription is disrupted following infection.
Authors
- Guijun Chen
- Erlin Wang (ORCID: https://orcid.org/0000-0001-7250-0483)
- Feng Xiong (ORCID: https://orcid.org/0000-0001-7051-6668)
- Jumin Zhou (ORCID: https://orcid.org/0000-0003-1389-1087)
- Hai-Bin Qin
- Wenbo Zeng (ORCID: https://orcid.org/0000-0002-1334-2726)
- Hui Zhang (ORCID: https://orcid.org/0000-0001-5683-5566)
- Xia Cao (ORCID: https://orcid.org/0000-0002-0453-9615)
- Kangning Chen (ORCID: https://orcid.org/0000-0002-0776-6709)
- Long-ding Liu (ORCID: https://orcid.org/0000-0001-8335-5613)
- Liping Yang (ORCID: https://orcid.org/0000-0001-6560-0478)
- Xiaoli Ren (ORCID: https://orcid.org/0009-0005-1656-0840)
- Nigel W. Fraser
- Min‐Hua Luo (ORCID: https://orcid.org/0000-0001-9352-0643)
- Mengqiu Yin
- Hansong Qi
Institutions
- Kunming Institute of Zoology (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Kunming Medical University (CN)
- Sichuan Agricultural University (CN)
- Wuhan Institute of Physics and Mathematics (CN)
- Wuhan Institute of Virology (CN)
- First Affiliated Hospital of Kunming Medical University (CN)
- University of Chinese Academy of Sciences (CN)
- University of Pennsylvania (US)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114792
- Citations
- 2
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.48
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- West Light Foundation of the Chinese Academy of Sciences
- National Natural Science Foundation of China-Yunnan Joint Fund