title: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2.
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.
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. chenjing519@126.com.|Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. chenjing519@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. shixibao@aliyun.com.|College of Life Sciences, Henan Normal University, Xinxiang 453007, China. shixibao@aliyun.com.
authors.forename: Xibao
authors.initials: X
authors.lastname: Shi
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang 453007, China. zhangxiaozhuan0103@126.com.
authors.forename: Xiaozhuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. nongkewangli@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. luojun593@aliyun.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. xingguangxu@163.com.
authors.forename: Guangxu
authors.initials: G
authors.lastname: Xing
authors.affiliation: Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. rgd999@163.com.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Deng
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang 453007, China. yanghong@htu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Henan Normal University, Xinxiang 453007, China. Ljt66882004@126.com.
authors.forename: Jinting
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Bioengineering, Zhengzhou University, Zhengzhou 450000, China. pingaw@126.com.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China. zhanggaiping2003@163.com.|Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China. zhanggaiping2003@163.com.|College of Veterinary Medicine and Animal Science, Henan Agricultural University, Zhengzhou 450002, China. zhanggaiping2003@163.com.
authors.forename: Gaiping
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002522:Chlorocebus aethiops; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000502:physiology*; D013552:Swine; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D060565:Argonaute Proteins; D017361:Viral Nonstructural Proteins
keywords: Ago-2; RNA silencing; non-structure protein 1α (nsp1α); nsp11; porcine reproductive and respiratory syndrome virus (PRRSV)