B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation

Kun Zhang, Dong Wen Lv, Renfeng Li

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Epstein-Barr virus (EBV) in tumor cells is predominately in the latent phase, but the virus can undergo lytic reactivation in response to various stimuli. However, the cellular factors that control latency and lytic replication are poorly defined. In this study, we demonstrated that a cellular factor, PIAS1, restricts EBV lytic replication. PIAS1 depletion significantly facilitated EBV reactivation, while PIAS1 reconstitution had the opposite effect. Remarkably, we found that various lytic triggers promote caspase-dependent cleavage of PIAS1 to antagonize PIAS1-mediated restriction and that caspase inhibition suppresses EBV replication through blocking PIAS1 cleavage. We further demonstrated that a cleavage-resistant PIAS1 mutant suppresses EBV replication upon B cell receptor activation. Mechanistically, we demonstrated that PIAS1 acts as an inhibitor for transcription factors involved in lytic gene expression. Collectively, these results establish PIAS1 as a key regulator of EBV lytic replication and uncover a mechanism by which EBV exploits apoptotic caspases to antagonize PIAS1-mediated restriction. The life cycle of Epstein-Barr virus (EBV) is tightly regulated by cellular factors. Zhang et al. identify PIAS1 as a critical host factor that suppresses EBV lytic replication. Upon B cell receptor activation or chemical perturbation, EBV hijacks host caspases to cleave and inactivate PIAS1 for efficient replication.

Original languageEnglish (US)
Pages (from-to)3445-3457
Number of pages13
JournalCell Reports
Volume21
Issue number12
DOIs
StatePublished - Dec 19 2017
Externally publishedYes

Keywords

  • apoptosis
  • B cell receptor activation
  • caspase
  • cleavage
  • Epstein-Barr virus
  • Kaposi's sarcoma-associated herpesvirus
  • latency
  • lytic induction
  • PIAS1
  • reactivation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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