ICP22-defined condensates mediate RNAPII deubiquitylation by UL36 and promote HSV-1 transcription
Year: 2024
Type: article
Abstract: 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.
Source: Cell Reports
Institutions: Kunming Institute of Zoology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, CAS, Sichuan Agricultural University, Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming Medical University, First Affiliated Hospital of Kunming Medical University, University of Pennsylvania
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
OpenAlex ID: W4403252613