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KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control

Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School and Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ 07103, USA
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Academic Editor: Zhi-Ming Zheng
Viruses 2015, 7(1), 72-109; https://doi.org/10.3390/v7010072
Received: 18 September 2014 / Accepted: 30 December 2014 / Published: 12 January 2015
(This article belongs to the Special Issue Kaposi's Sarcoma-Associated Herpesvirus)
In Kaposi’s sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is the lytic switch for reactivation. Rta transactivates essential genes via interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and the viral Mta protein. Given that robust viral reactivation would facilitate antiviral responses and culminate in host cell lysis, regulation of Rta’s expression and function is a major determinant of the latent-lytic balance and the fate of infected cells. Our lab recently showed that Rta transactivation requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest that proline‑directed phosphorylation regulates Rta by licensing binding to Pin1. Despite Pin1’s ability to stimulate Rta transactivation, unchecked Pin1 activity inhibited virus production. Dysregulation of Pin1 is implicated in human cancers, and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1 is a molecular timer that can regulate the balance between viral lytic gene expression and host cell lysis. Intriguing scenarios for Pin1’s underlying activities, and the potential broader significance for isomerization of Rta and reactivation, are highlighted. View Full-Text
Keywords: Kaposi’s sarcoma-associated Herpesvirus; Human herpesvirus-8; herpesvirus; reactivation; Rta; transcriptional activation; Pin1; Peptidyl-prolyl cis/trans isomerase Kaposi’s sarcoma-associated Herpesvirus; Human herpesvirus-8; herpesvirus; reactivation; Rta; transcriptional activation; Pin1; Peptidyl-prolyl cis/trans isomerase
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Guito, J.; Lukac, D.M. KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control. Viruses 2015, 7, 72-109.

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