Abstract
The ubiquitin–proteasome system (UPS) serves as the major intracellular pathway for protein degradation and plays crucial roles in several cellular processes. However, little is known about the potential actions of the UPS during fish virus infection. In this study, we elucidated the possible roles of UPS in the life cycle of Singapore grouper iridovirus (SGIV); a large DNA virus that usually causes serious systemic diseases with high mortality in groupers. Data from transcriptomic analysis of differentially expressed genes illustrated that expression of 65 genes within the UPS pathway, including ubiquitin encoding, ubiquitination, deubiquitination, and proteasome, were up- or down-regulated during SGIV infection. Using different proteasome inhibitors, inhibition of the proteasome decreased SGIV replication in vitro, accompanied by inhibition of virus assembly site formation, and viral gene transcription and protein transportation. Over-expression of ubiquitin partly rescued the inhibitory effect of ubiquitin inhibitor on SGIV replication, suggesting that UPS was required for fish iridovirus infection in vitro. Viral or host proteins regulated by proteasome inhibition during SGIV infection were investigated with two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Sixty-two differentially expressed proteins, including 15 viral and 47 host proteins, were identified after SGIV infection. The host proteins were involved in ubiquitin-mediated protein degradation, metabolism, cytoskeleton, macromolecular biosynthesis, and signal transduction. Among them, 11 proteins were negatively regulated upon MG132 treatment during SGIV infection. This is believed to be the first study to provide evidence that UPS was essential for fish virus infection and replication.
Highlights
The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation pathway and plays crucial roles in a variety of fundamental cellular processes, including regulation of gene transcription, cell cycle progression, autophagy, development and differentiation, and modulation of the immune and inflammatory responses (Glickman and Ciechanover, 2002; Wertz and Dixit, 2008; Zhao and Goldberg, 2016)
To unravel crucial cellular factors involved in Singapore grouper iridovirus (SGIV) replication, the differentially expressed cellular genes during virus infection were identified with RNA-Seq analysis
Sixty-four grouper genes related to the ubiquitin–proteasome system (UPS) components were differently regulated at the different stages of SGIV infection
Summary
The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation pathway and plays crucial roles in a variety of fundamental cellular processes, including regulation of gene transcription, cell cycle progression, autophagy, development and differentiation, and modulation of the immune and inflammatory responses (Glickman and Ciechanover, 2002; Wertz and Dixit, 2008; Zhao and Goldberg, 2016). UPS Is Required for SGIV Replication infection by affecting viral entry, gene transcription, assembly, release and immune evasion (Banks et al, 2003; Wang et al, 2016; Casorla-Pérez et al, 2017). Inhibition of proteasome activity prevents viral DNA replication and the formation of virus assembly sites during vaccinia virus (VACV) replication (Satheshkumar et al, 2009). Exploration of the molecular mechanism by which the UPS regulates viral replication will provide an alternative potential target for antiviral therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
