B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation
Summary: 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 cellu...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717317369 |
| _version_ | 1819010278729187328 |
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| author | Kun Zhang Dong-Wen Lv Renfeng Li |
| author_facet | Kun Zhang Dong-Wen Lv Renfeng Li |
| author_sort | Kun Zhang |
| collection | DOAJ |
| description | Summary: 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. Keywords: Epstein-Barr virus, Kaposi’s sarcoma-associated herpesvirus, latency, reactivation, B cell receptor activation, lytic induction, caspase, PIAS1, cleavage, apoptosis |
| first_indexed | 2024-12-21T01:09:44Z |
| format | Article |
| id | doaj.art-4e78ec2a51454739aaf62d682d650908 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T01:09:44Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4e78ec2a51454739aaf62d682d6509082022-12-21T19:20:57ZengElsevierCell Reports2211-12472017-12-01211234453457B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus ReactivationKun Zhang0Dong-Wen Lv1Renfeng Li2Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23298, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23298, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA; Corresponding authorSummary: 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. Keywords: Epstein-Barr virus, Kaposi’s sarcoma-associated herpesvirus, latency, reactivation, B cell receptor activation, lytic induction, caspase, PIAS1, cleavage, apoptosishttp://www.sciencedirect.com/science/article/pii/S2211124717317369 |
| spellingShingle | Kun Zhang Dong-Wen Lv Renfeng Li B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation Cell Reports |
| title | B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation |
| title_full | B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation |
| title_fullStr | B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation |
| title_full_unstemmed | B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation |
| title_short | B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation |
| title_sort | b cell receptor activation and chemical induction trigger caspase mediated cleavage of pias1 to facilitate epstein barr virus reactivation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717317369 |
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