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IP-10 Gene Transcription by Virus in Astrocytes Requires Cooperation of ISRE with Adjacent κB Site but Not IRF-1 or Viral Transcription

1998; Mary Ann Liebert, Inc.; Volume: 18; Issue: 11 Linguagem: Inglês

10.1089/jir.1998.18.987

1557-7465

Gaihua Cheng, AHAMED S.M.I. NAZAR, Hyun S. Shin, Padmavathy Vanguri, Moon L. Shin,

NF-κB Signaling Pathways

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.