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Viruses 2015, 7(10), 5539-5552; doi:10.3390/v7102893

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

1
College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China
2
Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China
3
College of Life Sciences, Henan Normal University, Xinxiang 453007, China
4
Department of Bioengineering, Zhengzhou University, Zhengzhou 450000, China
5
College of Veterinary Medicine and Animal Science, Henan Agricultural University, Zhengzhou 450002, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 3 August 2015 / Revised: 25 September 2015 / Accepted: 8 October 2015 / Published: 23 October 2015
(This article belongs to the Section Animal Viruses)
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Abstract

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. View Full-Text
Keywords: porcine reproductive and respiratory syndrome virus (PRRSV); RNA silencing; non-structure protein 1α (nsp1α); nsp11; Ago-2 porcine reproductive and respiratory syndrome virus (PRRSV); RNA silencing; non-structure protein 1α (nsp1α); nsp11; Ago-2
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chen, J.; Shi, X.; Zhang, X.; Wang, L.; Luo, J.; Xing, G.; Deng, R.; Yang, H.; Li, J.; Wang, A.; Zhang, G. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2. Viruses 2015, 7, 5539-5552.

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