Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2

Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral i...

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Main Authors: Jing Chen, Xibao Shi, Xiaozhuan Zhang, Li Wang, Jun Luo, Guangxu Xing, Ruiguang Deng, Hong Yang, Jinting Li, Aiping Wang, Gaiping Zhang
Format: Article
Language:English
Published: MDPI AG 2015-10-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/7/10/2893
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author Jing Chen
Xibao Shi
Xiaozhuan Zhang
Li Wang
Jun Luo
Guangxu Xing
Ruiguang Deng
Hong Yang
Jinting Li
Aiping Wang
Gaiping Zhang
author_facet Jing Chen
Xibao Shi
Xiaozhuan Zhang
Li Wang
Jun Luo
Guangxu Xing
Ruiguang Deng
Hong Yang
Jinting Li
Aiping Wang
Gaiping Zhang
author_sort Jing Chen
collection DOAJ
description Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.
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spelling doaj.art-e2fa229804f749729c533dcca84b59fe2022-12-22T01:35:06ZengMDPI AGViruses1999-49152015-10-017105539555210.3390/v7102893v7102893Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2Jing Chen0Xibao Shi1Xiaozhuan Zhang2Li Wang3Jun Luo4Guangxu Xing5Ruiguang Deng6Hong Yang7Jinting Li8Aiping Wang9Gaiping Zhang10College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, ChinaHenan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, ChinaCollege of Life Sciences, Henan Normal University, Xinxiang 453007, ChinaHenan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, ChinaHenan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, ChinaHenan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, ChinaHenan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, ChinaCollege of Life Sciences, Henan Normal University, Xinxiang 453007, ChinaCollege of Life Sciences, Henan Normal University, Xinxiang 453007, ChinaDepartment of Bioengineering, Zhengzhou University, Zhengzhou 450000, ChinaCollege of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, ChinaPorcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process.http://www.mdpi.com/1999-4915/7/10/2893porcine reproductive and respiratory syndrome virus (PRRSV)RNA silencingnon-structure protein 1α (nsp1α)nsp11Ago-2
spellingShingle Jing Chen
Xibao Shi
Xiaozhuan Zhang
Li Wang
Jun Luo
Guangxu Xing
Ruiguang Deng
Hong Yang
Jinting Li
Aiping Wang
Gaiping Zhang
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
Viruses
porcine reproductive and respiratory syndrome virus (PRRSV)
RNA silencing
non-structure protein 1α (nsp1α)
nsp11
Ago-2
title Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
title_full Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
title_fullStr Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
title_full_unstemmed Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
title_short Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2
title_sort porcine reproductive and respiratory syndrome virus prrsv inhibits rna mediated gene silencing by targeting ago 2
topic porcine reproductive and respiratory syndrome virus (PRRSV)
RNA silencing
non-structure protein 1α (nsp1α)
nsp11
Ago-2
url http://www.mdpi.com/1999-4915/7/10/2893
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