Differential host cell gene expression and regulation of cell cycle progression by nonstructural protein 11 of porcine reproductive and respiratory syndrome virus.
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-κ B 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.
Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA ; Department of Pathobiology, University of Pennsylvania, 380 South University Avenue, Philadelphia, PA 19104, USA.
Yan
Y
Sun
Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
Dong
0000-0003-3331-3268
D
Li
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Sumanprava
0000-0003-1218-3329
S
Giri
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Supriya G
SG
Prasanth
Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
Dongwan
0000-0002-6730-9729
D
Yoo
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016899:Interferon-beta / Q000235:genetics; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics* / Q000472:pathogenicity; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis*; D014779:Virus Replication / Q000235:genetics
D018797:Cell Cycle Proteins; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta