1. Academic Validation
  2. The S-Phase Arrest of Host Cells Caused by an Alpha-Herpesvirus Genome Replication Facilitates Viral Recruitment of RNA Polymerase II to Transcribe Viral Genes

The S-Phase Arrest of Host Cells Caused by an Alpha-Herpesvirus Genome Replication Facilitates Viral Recruitment of RNA Polymerase II to Transcribe Viral Genes

  • Cell Prolif. 2025 Jan 27:e13811. doi: 10.1111/cpr.13811.
Qiqi Yang 1 2 3 4 Ying Wu 1 2 3 4 Mingshu Wang 1 2 3 4 Shun Chen 1 2 3 4 Renyong Jia 1 2 3 4 Qiao Yang 1 2 3 4 Dekang Zhu 1 2 3 4 Mafeng Liu 1 2 3 4 Xinxin Zhao 1 2 3 4 Shaqiu Zhang 1 2 3 4 Juan Huang 1 2 3 4 Xumin Ou 1 2 3 4 Di Sun 1 2 3 4 Bin Tian 1 2 3 4 Yu He 1 2 3 4 Zhen Wu 1 2 3 4 Anchun Cheng 1 2 3 4
Affiliations

Affiliations

  • 1 Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu, China.
  • 2 International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu, China.
  • 3 Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, China.
  • 4 Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang, China.
Abstract

Herpesviruses rely on host RNA polymerae II (RNA Pol II) for their mRNA transcription, yet the mechanisms of which has been poorly defined, while certain herpesviruses can enhance viral gene transcription by altering the RNA Pol II location, modulating its phosphorylation, or directly interacting with RNA Pol II. However, the influence of herpesviruses on RNA Pol II transcription extends beyond these direct effects. Here, we present a novel mechanism by which the host cell cycle regulates viral gene transcription via RNA Pol II during Infection by Anatid Herpesvirus 1 (AnHV-1), an avian alpha-herpesvirus. The results demonstrated that the formation of viral replication compartments (vRCs) and the subsequent recruitment of RNA pol II are positively correlated with AnHV-1 DNA synthesis. As viral DNA replication progresses, host cells are arrested in the S phase, which not only halts host gene transcription but also facilitates viral transcription. This cell cycle arrest in the S phase promotes viral DNA (vDNA) synthesis and vRC formation, which further enhances the preferential recruitment of RNA Pol II to viral promoters, enabling efficient viral gene transcription. We propose that this S phase arrest and the hijacking of RNA Pol II represent a novel mechanism by which AnHV-1 enhances viral transcription, offering a unique survival strategy compared to the known strategy in herpesviruses. These findings expand our understanding of herpesvirus-host interactions and highlight potential targets for Antiviral strategies.

Keywords

AnHV‐1; RNA polymerase II; cell cycle; gene transcription; genome replication.

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