IP-10 gene transcription by virus in astrocytes requires cooperation of ISRE with adjacent kappaB site but not IRF-1 or viral transcription

J Interferon Cytokine Res. 1998 Nov;18(11):987-97. doi: 10.1089/jir.1998.18.987.

Abstract

Transcription of the IP-10 gene requires interferon (IFN)-stimulated response element (ISRE) and kappaB sites to be induced by lipopolysaccharide (LPS), IFN-gamma, virus, and poly(I:C). A requirement for Stat1 binding to ISRE for IFN-gamma and IFN regulatory factor-1 (IRF-1) binding to ISRE for LPS, poly(I:C), and virus has been reported. We investigated whether viral transcription is required for IP-10 induction and how ISRE interacts with IRF-1 and with two kappaB sites. IP-10 mRNA was induced by Newcastle disease virus and Sendai virus in rat astrocytes and the human astrocytoma U251 cell line. IP-10 was also induced by UV-irradiated virus, which is unable to carry out viral transcription. The minimal IP-10 virus response element (VRE) consists of an ISRE and adjacent kappaB site between -236 and -153, to which p50/p65 NF-kappaB proteins and IRF-like proteins bind. Virus induced NF-kappaB binding to an isolated kappaB sequence adjacent to ISRE. However, no protein binding to isolated ISRE was induced by virus. Virus also induced IP-10 in cells expressing a defective IRF-1 gene. Therefore, effective ISRE activity of IP-10 VRE may require an IRF-like protein binding, which is enhanced by an NF-kappaB heterodimer binding to an adjacent KB site. IRF-1 is not required for virus-induced IP-10 gene expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Astrocytes / virology
  • Base Sequence
  • Cell Line
  • Chemokine CXCL10
  • Chemokines, CXC / genetics*
  • Humans
  • Interferon-gamma / genetics*
  • Interferon-gamma / pharmacology
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • Newcastle disease virus / genetics
  • RNA, Viral / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Respirovirus / genetics
  • Response Elements*
  • Transcription Factors / genetics
  • Transcription, Genetic*
  • Virus Replication / drug effects*

Substances

  • Chemokine CXCL10
  • Chemokines, CXC
  • NF-kappa B
  • RNA, Viral
  • Transcription Factors
  • Interferon-gamma