1. Peroxisomes support human herpesvirus 8 latency by stabilizing the viral oncogenic protein vFLIP via the MAVS-TRAF complex.
- Author
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Choi YB, Choi Y, and Harhaj EW
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Autophagy, Cell Line, Gene Knockout Techniques, HEK293 Cells, Herpesvirus 8, Human genetics, Herpesvirus 8, Human immunology, Humans, Immunoblotting, Lymphoma, B-Cell pathology, Peroxisomes metabolism, Peroxisomes virology, Real-Time Polymerase Chain Reaction, Tumor Cells, Cultured, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins genetics, Viral Proteins genetics, Adaptor Proteins, Signal Transducing metabolism, Herpesvirus 8, Human physiology, Peroxisomes physiology, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins metabolism, Viral Proteins metabolism, Virus Latency physiology
- 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., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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