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The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication

Rabies virus (RABV) matrix (M) protein plays several important roles during RABV infection. Although previous studies have assessed the functions of M through gene rearrangements, this interferes with the position of other viral proteins. In this study, we attenuated M expression through deoptimizin...

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Autores principales: Luo, Jun, Zhang, Yue, Zhang, Qiong, Wu, Yuting, Zhang, Boyue, Mo, Meijun, Tian, Qin, Zhao, Jing, Mei, Mingzhu, Guo, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019236/
https://www.ncbi.nlm.nih.gov/pubmed/31861477
http://dx.doi.org/10.3390/v12010004
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author Luo, Jun
Zhang, Yue
Zhang, Qiong
Wu, Yuting
Zhang, Boyue
Mo, Meijun
Tian, Qin
Zhao, Jing
Mei, Mingzhu
Guo, Xiaofeng
author_facet Luo, Jun
Zhang, Yue
Zhang, Qiong
Wu, Yuting
Zhang, Boyue
Mo, Meijun
Tian, Qin
Zhao, Jing
Mei, Mingzhu
Guo, Xiaofeng
author_sort Luo, Jun
collection PubMed
description Rabies virus (RABV) matrix (M) protein plays several important roles during RABV infection. Although previous studies have assessed the functions of M through gene rearrangements, this interferes with the position of other viral proteins. In this study, we attenuated M expression through deoptimizing its codon usage based on codon pair bias in RABV. This strategy more objectively clarifies the role of M during virus infection. Codon-deoptimized M inhibited RABV replication during the early stages of infection, but enhanced viral titers at later stages. Codon-deoptimized M also inhibited genome synthesis at early stage of infection and increased the RABV transcription rates. Attenuated M through codon deoptimization enhanced RABV glycoprotein expression following RABV infection in neuronal cells, but had no influence on the cell-to-cell spread of RABV. In addition, codon-deoptimized M virus induced higher levels of apoptosis compared to the parental RABV. These results indicate that codon-deoptimized M increases glycoprotein expression, providing a foundation for further investigation of the role of M during RABV infection.
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spelling pubmed-70192362020-03-04 The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication Luo, Jun Zhang, Yue Zhang, Qiong Wu, Yuting Zhang, Boyue Mo, Meijun Tian, Qin Zhao, Jing Mei, Mingzhu Guo, Xiaofeng Viruses Article Rabies virus (RABV) matrix (M) protein plays several important roles during RABV infection. Although previous studies have assessed the functions of M through gene rearrangements, this interferes with the position of other viral proteins. In this study, we attenuated M expression through deoptimizing its codon usage based on codon pair bias in RABV. This strategy more objectively clarifies the role of M during virus infection. Codon-deoptimized M inhibited RABV replication during the early stages of infection, but enhanced viral titers at later stages. Codon-deoptimized M also inhibited genome synthesis at early stage of infection and increased the RABV transcription rates. Attenuated M through codon deoptimization enhanced RABV glycoprotein expression following RABV infection in neuronal cells, but had no influence on the cell-to-cell spread of RABV. In addition, codon-deoptimized M virus induced higher levels of apoptosis compared to the parental RABV. These results indicate that codon-deoptimized M increases glycoprotein expression, providing a foundation for further investigation of the role of M during RABV infection. MDPI 2019-12-18 /pmc/articles/PMC7019236/ /pubmed/31861477 http://dx.doi.org/10.3390/v12010004 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Luo, Jun
Zhang, Yue
Zhang, Qiong
Wu, Yuting
Zhang, Boyue
Mo, Meijun
Tian, Qin
Zhao, Jing
Mei, Mingzhu
Guo, Xiaofeng
The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title_full The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title_fullStr The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title_full_unstemmed The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title_short The Deoptimization of Rabies Virus Matrix Protein Impacts Viral Transcription and Replication
title_sort deoptimization of rabies virus matrix protein impacts viral transcription and replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019236/
https://www.ncbi.nlm.nih.gov/pubmed/31861477
http://dx.doi.org/10.3390/v12010004
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