@article{e01da8f211d44d029e67c4ae00d95090,
title = "Peroxisomes support human herpesvirus 8 latency by stabilizing the viral oncogenic protein vFLIP via the MAVS-TRAF complex",
abstract = "Human herpesvirus 8 (HHV-8) is causally related to human malignancies. HHV-8 latent viral FLICE-inhibitory protein (vFLIP) is a viral oncoprotein that is linked to pathogenesis, but how its expression is regulated is largely unknown. In an attempt to understand the role of the mitochondrial antiviral signaling (MAVS) adaptor in HHV-8 infection, we discovered that vFLIP expression was post-translationally up-regulated by the MAVS signaling complex on peroxisomes. Furthermore, we demonstrated that vFLIP could be targeted to the peroxisomes, where it was oncogenically active, in a PEX19-dependent manner. Targeted disruption of vFLIP and MAVS interaction resulted in a decrease in vFLIP expression and selectively promoted death of latently HHV-8-infected cells, providing therapeutic potential for treating HHV-8 diseases. Collectively, our experimental results suggest novel involvement of peroxisomes and MAVS in the stabilization of vFLIP and thereby in the establishment or maintenance of HHV-8 latency and associated pathogenesis.",
author = "Choi, {Young Bong} and Yeeun Choi and Harhaj, {Edward William}",
note = "Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases grant (R21AI117168 to YBC; https://www.niaid.nih.gov). In addition, this work was supported in part by a 2016-2017 developmental grant from the Johns Hopkins University (JHU) Center for AIDS Research, a National Institute of Health (NIH) funded program (P30AI094189 to YBC; http://hopkinscfar.org), the Maryland Cigarette Restitution Fund Research Grant to the Johns Hopkins Medical Institutions (FY16 to YBC; http://crf.maryland.gov), and an NIH Shared Instrumentation grant (S10OD016374 to the JHU Microscope Facility). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Dr. Elana S. Ehrlich for anti-vFLIP antibody, and Drs. Joanna Shisler and Yanjin Zhang for the gifts of plasmids pcDNA3_HA-MC159 and pVenus N1-RRV vFLIP, respectively. We thank Dr. John Nicholas for critically proofreading the manuscript. Publisher Copyright: {\textcopyright} 2018 Choi et al. http://creativecommons.org/licenses/by/4.0/",
year = "2018",
month = may,
doi = "10.1371/journal.ppat.1007058",
language = "English (US)",
volume = "14",
journal = "PLoS pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "5",
}