Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation

FEBS Lett. 2006 Dec 22;580(30):6807-12. doi: 10.1016/j.febslet.2006.11.046. Epub 2006 Nov 27.

Abstract

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chemokines / biosynthesis*
  • Enzyme Activation
  • Gene Expression
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic / genetics
  • SARS Virus / genetics
  • SARS Virus / metabolism*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / metabolism*

Substances

  • Chemokines
  • NF-kappa B
  • ORF3A protein, SARS coronavirus
  • Viral Matrix Proteins
  • Viral Proteins
  • Viral Structural Proteins
  • sars7a protein, SARS virus
  • JNK Mitogen-Activated Protein Kinases