Nephelus coioides) brain cells; on the other hand, the detailed mechanisms of this action remain unknown. In this study, we discovered that the host translation element, polyadenylate P2Y14 Receptor list binding protein (PABP), can be a crucial target for the duration of NNV takeover of host translation machinery. Also, ectopic expression of NNV coat protein is adequate to trigger nuclear translocalization and degradation of PABP, followed by translation shutoff. A PAK4 Accession direct interaction in between NNV coat protein and PABP was demonstrated, and this binding demands the NNV coat protein N-terminal shell domain and PABP prolinerich linker region. Notably, we also showed that degradation of PABP in the course of later stages of infection is mediated by the ubiquitin-proteasome pathway. Therefore, our study reveals that the NNV coat protein hijacks host PABP, causing its relocalization towards the nucleus and advertising its degradation to stimulate host translation shutoff.Value Globally, far more than 200 species of aquacultured and wild marine fish are susceptible to NNV infection. Devastating outbreaks of this virus have been accountable for massive financial harm within the aquaculture sector, however the molecular mechanisms by which NNV impacts its host stay largely unclear. In this study, we show that NNV hijacks translation in host brain cells, with all the viral coat protein binding to host PABP to market its nuclear translocalization and degradation. This previously unknown mechanism of NNV-induced host translation shutoff tremendously enhances the understanding of NNV pathogenesis and offers beneficial insights and novel tools for development of NNV remedies, for instance the use of orange-spotted grouper brain cells as an in vitro model program. Key phrases nervous necrosis virus, coat protein, polyadenylate binding protein,Citation Cheng C-A, Luo J-M, Chiang M-H, Fang K-Y, Li C-H, Chen C-W, Wang Y-S, Chang C-Y. 2021. Nervous necrosis virus coat protein mediates host translation shutoff via nuclear translocalization and degradation of polyadenylate binding protein. J Virol 95: e02364-20. Editor J.-H. James Ou, University of Southern California Copyright 2021 American Society for Microbiology. All Rights Reserved. Address correspondence to Chi-Yao Chang, [email protected] shutoff, nuclear translocalization iral nervous necrosis (1), otherwise generally known as viral encephalopathy and retinopathy (two), is definitely an infectious neuropathological illness that impacts extra than 200 species of farmed and wild marine fish worldwide, with nearly one hundred mortality observed in affected larvae and juvenile fish (3). The disease is brought on by infection with nervous necrosis virus (NNV), which belongs towards the genus Betanodavirus with the family Nodaviridae. NNV has aSeptember 2021 Volume 95 Problem 17 e02364-20 Journal of VirologyVReceived 10 December 2020 Accepted eight June 2021 Accepted manuscript posted on the web 16 June 2021 Published 10 Augustjvi.asm.orgCheng et al.Journal of Virologysmall (about 25 nm), nonenveloped icosahedral structure and consists of a bipartite, linear, positive-sense, single-stranded RNA genome composed of RNA1 and RNA2. These RNAs encode an RNA-dependent RNA polymerase (RdRp) and also a coat protein, respectively (4). Furthermore, a subgenomic transcript of RNA1, referred to as RNA3, encodes protein B2, which is identified to antagonize host RNA interference by binding to double-stranded RNA (dsRNA) through virus multiplication (five, six). Importantly, the NNV RNAs each include a cap.