An alternative Kaposi's sarcoma-associated herpesvirus replication program triggered by host cell apoptosis.

Journal of Virology
Alka PrasadS Zeichner

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several neoplastic diseases: Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV replicates actively, via a controlled gene expression program, but can also remain latent. It had been thought that the transition from latent to lytic replication was controlled exclusively by the replication and transcription activator protein RTA (open reading frame 50 [ORF50] gene product). A dominant-negative (DN) ORF50 mutant, ORF50ΔSTAD, blocks gene expression and replication. We produced a PEL cell line derivative containing both latent KSHV genomes and an inducible ORF50ΔSTAD. We unexpectedly found that induction of apoptosis triggered high-level viral replication, even when DN ORF50ΔSTAD was present, suggesting that apoptosis triggers KSHV replication through a distinct RTA-independent pathway. We verified that apoptosis triggers KSHV replication independent of RTA using ORF50 small interfering RNA (siRNA) and also showed that caspase activity is required to trigger KSHV replication. We showed that when apoptosis triggers KSHV replication, the kinetics of late gene expression is accelerated by 12 to 24 h and that virus produced foll...Continue Reading

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Citations

Aug 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Te DuBernard Roizman
May 20, 2015·Retrovirology·Sohrab Z KhanSteven L Zeichner
Sep 2, 2016·The Journal of Clinical Investigation·Dirk P Dittmer, Blossom Damania
Jul 20, 2018·Journal of Virology·Tate Tabtieng, Marta M Gaglia
May 10, 2016·F1000Research·Nathan J Dissinger, Blossom Damania
Aug 31, 2017·PLoS Pathogens·Alessandra De LeoPaul M Lieberman
Jul 26, 2013·Journal of Virology·Alka PrasadSteven L Zeichner
Sep 19, 2021·The FEBS Journal·Kwun Wah WenBlossom Damania
Jun 4, 2021·Pediatrics·Lisa BiswasSteven L Zeichner

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