Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2016 Feb 19

PMID 26891221

Citations 21

Authors

Giuseppe Balistreri

Johanna Viiliainen

Mikko Turunen

Raquel Diaz

Lauri Lyly

Pirita Pekkonen

Juha Rantala

Krista Ojala

Grzegorz Sarek

Mari Teesalu

Oxana Denisova

Karita Peltonen

Ilkka Julkunen

Markku Varjosalo

Denis Kainov

Olli Kallioniemi

Marikki Laiho

Jussi Taipale

Sampsa Hautaniemi

Paivi M Ojala

Affiliations

Soon will be listed here.

Abstract

Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.

Citing Articles

EZH2 Inhibition by DS3201 Triggers the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle and Potentiates the Effects Induced by SAHA in Primary Effusion Lymphoma Cells.

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Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein Represses Cellular MDM2 Expression via Suppressing the Sp1- and p53-Mediated Transactivation.

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