PMID:26512690

Citation	Chen, J, Shi, X, Zhang, X, Wang, L, Luo, J, Xing, G, Deng, R, Yang, H, Li, J, Wang, A and Zhang, G (2015) Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2. Viruses 7:5539-52
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.
Links	PubMed Online version:10.3390/v7102893
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
PIG:I3L6Y9		GO:0039537: suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway	ECO:0000314:		P		Figures 2 and 3 shows that Dicer is normally involved in the cellular defense against viruses. The expression of Dicer is shown in Figure 2 when the cell is placed under viral stress, and in Figure 3, the levels of the fragment of the porcine reproductive and respiratory syndrome virus (PRRSV) is shown to be lowered in the presence of Dicer. However, in Figure 1, PRRSV is shown to silence luciferase when gene that codes for luciferase is placed in the gene that codes for Dicer. In Figure 4, the PRRSV lowers the expression of Dicer and Ago-2 (both involved in the cellular defense mechanism against PRRSV) simultaneously when fully functional. The lowered expression is shown specifically in Figure 4.F.	complete CACAO 11121

References

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