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Function of Host Protein Staufen1 in Rabies Virus Replication

Rabies virus is a highly neurophilic negative-strand RNA virus with high lethality and remains a huge public health problem in developing countries to date. The double-stranded RNA-binding protein Staufen1 (STAU1) has multiple functions in RNA virus replication, transcription, and translation. Howev...

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Autores principales: Liu, Gaowen, Chen, Congjie, Xu, Ruixian, Yang, Ming, Han, Qinqin, Wang, Binghui, Song, Yuzhu, Xia, Xueshan, Zhang, Jinyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402631/
https://www.ncbi.nlm.nih.gov/pubmed/34452292
http://dx.doi.org/10.3390/v13081426
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author Liu, Gaowen
Chen, Congjie
Xu, Ruixian
Yang, Ming
Han, Qinqin
Wang, Binghui
Song, Yuzhu
Xia, Xueshan
Zhang, Jinyang
author_facet Liu, Gaowen
Chen, Congjie
Xu, Ruixian
Yang, Ming
Han, Qinqin
Wang, Binghui
Song, Yuzhu
Xia, Xueshan
Zhang, Jinyang
author_sort Liu, Gaowen
collection PubMed
description Rabies virus is a highly neurophilic negative-strand RNA virus with high lethality and remains a huge public health problem in developing countries to date. The double-stranded RNA-binding protein Staufen1 (STAU1) has multiple functions in RNA virus replication, transcription, and translation. However, its function in RABV infection and its mechanism of action are not clear. In this study, we investigated the role of host factor STAU1 in RABV infection of SH-SY-5Y cells. Immunofluorescence, TCID(50) titers, confocal microscopy, quantitative real-time PCR and Western blotting were carried out to determine the molecular function and subcellular distribution of STAU1 in these cell lines. Expression of STAU1 in SH-SY-5Y cells was down-regulated by RNA interference or up-regulated by transfection of eukaryotic expression vectors. The results showed that N proficiently colocalized with STAU1 in SH-SY-5Y at 36 h post-infection, and the expression level of STAU1 was also proportional to the time of infection. Down-regulation of STAU1 expression increased the number of Negri body-like structures, enhanced viral replication, and a caused 10-fold increase in viral titers. Meanwhile, N protein and G protein mRNA levels also accumulated gradually with increasing infection time, which implied that STAU1 inhibited rabies virus infection of SH-SY-5Y cells in vitro. In conclusion, our results provide important clues for the detailed replication mechanism of rabies virus and the discovery of therapeutic targets.
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spelling pubmed-84026312021-08-29 Function of Host Protein Staufen1 in Rabies Virus Replication Liu, Gaowen Chen, Congjie Xu, Ruixian Yang, Ming Han, Qinqin Wang, Binghui Song, Yuzhu Xia, Xueshan Zhang, Jinyang Viruses Article Rabies virus is a highly neurophilic negative-strand RNA virus with high lethality and remains a huge public health problem in developing countries to date. The double-stranded RNA-binding protein Staufen1 (STAU1) has multiple functions in RNA virus replication, transcription, and translation. However, its function in RABV infection and its mechanism of action are not clear. In this study, we investigated the role of host factor STAU1 in RABV infection of SH-SY-5Y cells. Immunofluorescence, TCID(50) titers, confocal microscopy, quantitative real-time PCR and Western blotting were carried out to determine the molecular function and subcellular distribution of STAU1 in these cell lines. Expression of STAU1 in SH-SY-5Y cells was down-regulated by RNA interference or up-regulated by transfection of eukaryotic expression vectors. The results showed that N proficiently colocalized with STAU1 in SH-SY-5Y at 36 h post-infection, and the expression level of STAU1 was also proportional to the time of infection. Down-regulation of STAU1 expression increased the number of Negri body-like structures, enhanced viral replication, and a caused 10-fold increase in viral titers. Meanwhile, N protein and G protein mRNA levels also accumulated gradually with increasing infection time, which implied that STAU1 inhibited rabies virus infection of SH-SY-5Y cells in vitro. In conclusion, our results provide important clues for the detailed replication mechanism of rabies virus and the discovery of therapeutic targets. MDPI 2021-07-22 /pmc/articles/PMC8402631/ /pubmed/34452292 http://dx.doi.org/10.3390/v13081426 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Gaowen
Chen, Congjie
Xu, Ruixian
Yang, Ming
Han, Qinqin
Wang, Binghui
Song, Yuzhu
Xia, Xueshan
Zhang, Jinyang
Function of Host Protein Staufen1 in Rabies Virus Replication
title Function of Host Protein Staufen1 in Rabies Virus Replication
title_full Function of Host Protein Staufen1 in Rabies Virus Replication
title_fullStr Function of Host Protein Staufen1 in Rabies Virus Replication
title_full_unstemmed Function of Host Protein Staufen1 in Rabies Virus Replication
title_short Function of Host Protein Staufen1 in Rabies Virus Replication
title_sort function of host protein staufen1 in rabies virus replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402631/
https://www.ncbi.nlm.nih.gov/pubmed/34452292
http://dx.doi.org/10.3390/v13081426
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