FUS Negatively Regulates Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression
AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi’s sarcoma. KSHV is also causally associated with the development of lymphoproliferative diseases, including primary effusion lymphoma (PEL). KSHV reactivation from latency plays an integral role in the progression to KSHV-associated disease as several lytic proteins have angiogenic and anti-apoptotic functions essential to the tumor microenvironment. Thus, restriction of KSHV reactivation represents an attractive therapeutic target. Here, we demonstrate that the cellular protein Fused-in-sarcoma (FUS) restricts KSHV lytic reactivation in PEL and in an epithelial cell-based model. Depletion of FUS significantly enhances viral mRNA and protein expression, resulting in increased viral replication and production of infectious virions. Chromatin immunoprecipitation analyses demonstrate that FUS is present at several KSHV lytic cycle genes during the latent stage of infection. We further demonstrate that FUS interacts with RNA polymerase II and negatively affects Serine-2 phosphorylation of its C-terminal domain at the KSHV RTA gene, decreasing nascent RNA synthesis. Knockdown of FUS increases transcription of RTA, thus driving enhanced expression of KSHV lytic genes. Collectively, these data reveal a novel role for FUS in regulating viral gene expression and are the first to demonstrate its role as a viral restriction factor. View Full-Text
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Dunker, W.; Song, Y.; Zhao, Y.; Karijolich, J. FUS Negatively Regulates Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression. Viruses 2018, 10, 359.
Dunker W, Song Y, Zhao Y, Karijolich J. FUS Negatively Regulates Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression. Viruses. 2018; 10(7):359.Chicago/Turabian Style
Dunker, William; Song, Yu; Zhao, Yang; Karijolich, John. 2018. "FUS Negatively Regulates Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression." Viruses 10, no. 7: 359.
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