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Title: Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation

Abstract

Nuclear factor-kappaB (NF-{kappa}B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-{kappa}B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-{kappa}B activation was characterized by translocation of NF-{kappa}B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-{kappa}B-regulated gene expression. NF-{kappa}B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-{kappa}B activation. Degradation of I{kappa}B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I{kappa}B{alpha} (I{kappa}B{alpha}DN) significantly suppressed NF-{kappa}B activation induced by PRRSV. However, I{kappa}B{alpha}DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-{kappa}B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-{kappa}B was activated by PRRSV infection. Moreover, NF-{kappa}B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-{kappa}B activation is a biologically significant aspect ofmore » PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV.« less

Authors:
 [1];  [2]
  1. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, MO 65211 (United States)
  2. Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, MO 65211 (United States) and Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, MO 65211 (United States). E-mail: KleiboekerS@Missouri.edu
Publication Date:
OSTI Identifier:
20779431
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 342; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2005.07.034; PII: S0042-6822(05)00452-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BIOLOGICAL STRESS; CELL PROLIFERATION; CYTOPLASM; DNA; MACROPHAGES; OXYGEN; PATHOGENESIS; PATHOLOGY; PROTEINS; RESPIRATORY SYSTEM DISEASES; TRANSLOCATION; VIRUSES

Citation Formats

Lee, Sang-Myeong, and Kleiboeker, Steven B. Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation. United States: N. p., 2005. Web. doi:10.1016/J.VIROL.2005.0.
Lee, Sang-Myeong, & Kleiboeker, Steven B. Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation. United States. doi:10.1016/J.VIROL.2005.0.
Lee, Sang-Myeong, and Kleiboeker, Steven B. Thu . "Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation". United States. doi:10.1016/J.VIROL.2005.0.
@article{osti_20779431,
title = {Porcine arterivirus activates the NF-{kappa}B pathway through I{kappa}B degradation},
author = {Lee, Sang-Myeong and Kleiboeker, Steven B.},
abstractNote = {Nuclear factor-kappaB (NF-{kappa}B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-{kappa}B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-{kappa}B activation was characterized by translocation of NF-{kappa}B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-{kappa}B-regulated gene expression. NF-{kappa}B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-{kappa}B activation. Degradation of I{kappa}B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I{kappa}B{alpha} (I{kappa}B{alpha}DN) significantly suppressed NF-{kappa}B activation induced by PRRSV. However, I{kappa}B{alpha}DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-{kappa}B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-{kappa}B was activated by PRRSV infection. Moreover, NF-{kappa}B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-{kappa}B activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV.},
doi = {10.1016/J.VIROL.2005.0},
journal = {Virology},
number = 1,
volume = 342,
place = {United States},
year = {Thu Nov 10 00:00:00 EST 2005},
month = {Thu Nov 10 00:00:00 EST 2005}
}