Abstract
Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) is a viral endoribonuclease with an unknown function. The regulation of cellular gene expression by nsp11 was examined by RNA microarrays using MARC-nsp11 cells constitutively expressing nsp11. In these cells, the interferon-β, interferon regulatory factor 3, and nuclear factor-κB activities were suppressed compared to those of parental cells, suggesting that nsp11 might serve as a viral interferon antagonist. Differential cellular transcriptome was examined using Affymetrix exon chips representing 28,536 transcripts, and after statistical analyses 66 cellular genes were shown to be upregulated and 104 genes were downregulated by nsp11. These genes were grouped into 5 major signaling pathways according to their functional relations: histone-related, cell cycle and DNA replication, mitogen activated protein kinase signaling, complement, and ubiquitin-proteasome pathways. Of these, the modulation of cell cycle by nsp11 was further investigated since many of the regulated genes fell in this particular pathway. Flow cytometry showed that nsp11 caused the delay of cell cycle progression at the S phase and the BrdU staining confirmed the cell cycle arrest in nsp11-expressing cells. The study provides insights into the understanding of specific cellular responses to nsp11 during PRRSV infection.
Highlights
Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant infectious diseases for the pig industry worldwide and causes severe economic losses [1]
Mutational studies using equine arteritis virus (EAV) nsp11, which is a homolog of PRRS virus (PRRSV) nsp11, show that three enzymatically catalytic sites reside in subdomain A, while two aspartic acids in subdomain B are responsible for the overall protein structure [16]
We provide the evidence that PRRSV nsp11 protein participates in modulating the cell cycle progression at the S phase
Summary
Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant infectious diseases for the pig industry worldwide and causes severe economic losses [1]. The etiological agent is PRRS virus (PRRSV), which belongs to the family Arteriviridae in the order Nidovirales [2] and possesses a single-stranded positive-sense RNA genome of 15.4 kb in size [3,4,5,6]. PP1a and PP1a/b are cotranslationally processed into 14 cleavage products. These products are nonstructural proteins (nsps) that are believed to participate in viral genome replication and subgenomic mRNA transcription [11,12,13]. Nsp is a 223 amino acid protein and contains a nidovirus-specific domain, termed NendoU, in the Cterminal region. In EAV, nsp plays a key role in viral RNA synthesis and it may be essential for PRRSV replication. PRRSV has been shown to modulate type I IFN response [17] and nsp has been suggested to participate in the modulation of IFN response [18]
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