1. Viral Manipulation of a Mechanoresponsive Signaling Axis Disassembles Processing Bodies.
- Author
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Castle EL, Robinson CA, Douglas P, Rinker KD, and Corcoran JA
- Subjects
- Actin Cytoskeleton metabolism, Actomyosin metabolism, Cell Shape physiology, Gene Expression Regulation genetics, Herpesvirus 8, Human genetics, Herpesvirus 8, Human metabolism, Host Microbial Interactions physiology, Humans, Sarcoma, Kaposi pathology, Sarcoma, Kaposi virology, Signal Transduction physiology, Viral Proteins genetics, Virus Replication physiology, Cell Transformation, Neoplastic pathology, Mechanotransduction, Cellular physiology, Processing Bodies metabolism, Viral Proteins metabolism, YAP-Signaling Proteins metabolism, rhoA GTP-Binding Protein metabolism
- Abstract
Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi's sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi's sarcoma, and a PB-regulating virus. The virus encodes kaposin B (KapB), which induces actin stress fibers (SFs) and cell spindling as well as PB disassembly. We now show that KapB-mediated PB disassembly requires actin rearrangements, RhoA effectors, and the mechanoresponsive transcription activator, YAP. Moreover, ectopic expression of active YAP or exposure of ECs to mechanical forces caused PB disassembly in the absence of KapB. We propose that the viral protein KapB activates a mechanoresponsive signaling axis and links changes in cell shape and cytoskeletal structures to enhanced inflammatory molecule expression using PB disassembly. Our work implies that cytoskeletal changes in other pathologies may similarly impact the inflammatory environment.
- Published
- 2021
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