title: TRIM5α Promotes Ubiquitination of Rta from Epstein-Barr Virus to Attenuate Lytic Progression.
abstract: Replication and transcription activator (Rta), a key protein expressed by Epstein-Barr virus (EBV) during the immediate-early stage of the lytic cycle, is responsible for the activation of viral lytic genes. In this study, GST-pulldown and coimmunoprecipitation assays showed that Rta interactsin vitroandin vivowith TRIM5α, a host factor known to be involved in the restriction of retroviral infections. Confocal microscopy results revealed that Rta colocalizes with TRIM5α in the nucleus during lytic progression. The interaction involves 190 amino acids in the N-terminal of Rta and the RING domain in TRIM5α, and it was further found that TRIM5α acts as an E3 ubiquitin ligase to promote Rta ubiquitination. Overexpression of TRIM5α reduced the transactivating capabilities of Rta, while reducing TRIM5α expression enhanced EBV lytic protein expression and DNA replication. Taken together, these results point to a critical role for TRIM5α in attenuating EBV lytic progression through the targeting of Rta for ubiquitination, and suggest that the restrictive capabilities of TRIM5α may go beyond retroviral infections.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University Taipei, Taiwan.
authors.forename: Hsiang-Hung
authors.initials: HH
authors.lastname: Huang
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University Taipei, Taiwan.
authors.forename: Chien-Sin
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Kaohsiung Medical University Hospital Kaohsiung, Taiwan.
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University Taipei, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Hsu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University Taipei, Taiwan.
authors.forename: Hsiao-Han
authors.initials: HH
authors.lastname: Tsai
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University Taoyuan, Taiwan.
authors.forename: Shih-Tung
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University Taipei, Taiwan.
authors.forename: Li-Kwan
authors.initials: LK
authors.lastname: Chang
keywords: Epstein–Barr virus; Rta; TRIM5α; ubiquitination; viral–host interactions