Cargando…

Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication

Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. Howeve...

Descripción completa

Detalles Bibliográficos
Autores principales: Hou, Shitong, Wang, Xiangwei, Ren, Shanhui, Meng, Xuelian, Yin, Xiangping, Zhang, Jie, Tarasiuk, Kazimierz, Pejsak, Zygmunt, Jiang, Tao, Mao, Ruoqing, Zhang, Yongguang, Sun, Yuefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894894/
https://www.ncbi.nlm.nih.gov/pubmed/35250927
http://dx.doi.org/10.3389/fmicb.2022.805606
_version_ 1784662788799463424
author Hou, Shitong
Wang, Xiangwei
Ren, Shanhui
Meng, Xuelian
Yin, Xiangping
Zhang, Jie
Tarasiuk, Kazimierz
Pejsak, Zygmunt
Jiang, Tao
Mao, Ruoqing
Zhang, Yongguang
Sun, Yuefeng
author_facet Hou, Shitong
Wang, Xiangwei
Ren, Shanhui
Meng, Xuelian
Yin, Xiangping
Zhang, Jie
Tarasiuk, Kazimierz
Pejsak, Zygmunt
Jiang, Tao
Mao, Ruoqing
Zhang, Yongguang
Sun, Yuefeng
author_sort Hou, Shitong
collection PubMed
description Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. However, only a few cell lines are sensitive to FMDV, and there is still a lot of room for improvement. Acetylation is an important post-translational modification, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). However, the study of the relationship between FMDV and HDACs is still unclear. HDAC9 belongs to the class II of HDACs family; in this study, HDAC9 knockout (KO) BHK-21 cells were successfully established using CRISPR/cas9 technology. The results of karyotype analysis, growth curve analysis, and morphological observation showed that the HDAC9 knockout cell line was stable in growth and morphological characteristics. After infection with FMDV, the expression of viral RNA and protein, viral titers, and the copies of viral RNA in HDAC9-KO cells were significantly higher than those in NC cells. Meanwhile, RNA-seq technology was used to sequence HDAC9-KO cells and NC cells infected and uninfected with FMDV. It was found that the differentially expressed innate immune factors containing NFKBIA, SOD2, IL2RG, BCL2L1, CXCL1/2/3, and IL1RAP have significantly enriched in the Jak-STAT, NOD-like receptor, Toll-like receptor, NF-κB, and MAPK signaling pathway. RT-qPCR was performed to detect the expression level of differentially expressed genes and showed consistency with the RNA-seq data. These results preliminarily reveal the role of HDAC9 in host antiviral innate immune response, and the HDAC9-KO cell line could also serve as a useful tool for FMDV research.
format Online
Article
Text
id pubmed-8894894
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88948942022-03-05 Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication Hou, Shitong Wang, Xiangwei Ren, Shanhui Meng, Xuelian Yin, Xiangping Zhang, Jie Tarasiuk, Kazimierz Pejsak, Zygmunt Jiang, Tao Mao, Ruoqing Zhang, Yongguang Sun, Yuefeng Front Microbiol Microbiology Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease that mainly infects cloven-hoofed animals. Propagation of FMDV by cell culture is an important method to preserve viral biological and antigenic characteristics, which is crucial in FMD monitoring and vaccine production. However, only a few cell lines are sensitive to FMDV, and there is still a lot of room for improvement. Acetylation is an important post-translational modification, which is dynamically regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). However, the study of the relationship between FMDV and HDACs is still unclear. HDAC9 belongs to the class II of HDACs family; in this study, HDAC9 knockout (KO) BHK-21 cells were successfully established using CRISPR/cas9 technology. The results of karyotype analysis, growth curve analysis, and morphological observation showed that the HDAC9 knockout cell line was stable in growth and morphological characteristics. After infection with FMDV, the expression of viral RNA and protein, viral titers, and the copies of viral RNA in HDAC9-KO cells were significantly higher than those in NC cells. Meanwhile, RNA-seq technology was used to sequence HDAC9-KO cells and NC cells infected and uninfected with FMDV. It was found that the differentially expressed innate immune factors containing NFKBIA, SOD2, IL2RG, BCL2L1, CXCL1/2/3, and IL1RAP have significantly enriched in the Jak-STAT, NOD-like receptor, Toll-like receptor, NF-κB, and MAPK signaling pathway. RT-qPCR was performed to detect the expression level of differentially expressed genes and showed consistency with the RNA-seq data. These results preliminarily reveal the role of HDAC9 in host antiviral innate immune response, and the HDAC9-KO cell line could also serve as a useful tool for FMDV research. Frontiers Media S.A. 2022-02-18 /pmc/articles/PMC8894894/ /pubmed/35250927 http://dx.doi.org/10.3389/fmicb.2022.805606 Text en Copyright © 2022 Hou, Wang, Ren, Meng, Yin, Zhang, Tarasiuk, Pejsak, Jiang, Mao, Zhang and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hou, Shitong
Wang, Xiangwei
Ren, Shanhui
Meng, Xuelian
Yin, Xiangping
Zhang, Jie
Tarasiuk, Kazimierz
Pejsak, Zygmunt
Jiang, Tao
Mao, Ruoqing
Zhang, Yongguang
Sun, Yuefeng
Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title_full Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title_fullStr Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title_full_unstemmed Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title_short Knockout of HDAC9 Gene Enhances Foot-and-Mouth Disease Virus Replication
title_sort knockout of hdac9 gene enhances foot-and-mouth disease virus replication
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894894/
https://www.ncbi.nlm.nih.gov/pubmed/35250927
http://dx.doi.org/10.3389/fmicb.2022.805606
work_keys_str_mv AT houshitong knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT wangxiangwei knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT renshanhui knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT mengxuelian knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT yinxiangping knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT zhangjie knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT tarasiukkazimierz knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT pejsakzygmunt knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT jiangtao knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT maoruoqing knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT zhangyongguang knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication
AT sunyuefeng knockoutofhdac9geneenhancesfootandmouthdiseasevirusreplication