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

Transcription of the IP-10 gene requires interferon (IFN)-stimulated respon se element (ISRE) and kappa B sites to be induced by lipopolysaccharide (LP S), IFN-gamma, virus, and poly(I:C), A requirement for Stat1 binding to ISR E 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 tra nscription is required for IP-10 induction and how ISRE interacts with IRF- 1 and with two kappa B sites, IP-10 mRNA was induced by Newcastle disease v irus and Sendai virus in rat astrocytes and the human astrocytoma U251 cell line. IF-10 was also induced by UV-irradiated virus, which is unable to ca rry out viral transcription. The minimal IF-10 virus response element (VRE) consists of an ISRE and adjacent kappa B site between -236 and -153, to wh ich p50/p65 NF-kappa B proteins and IRF-like proteins bind. Virus induced N F-kappa B binding to an isolated kappa B sequence adjacent to ISRE, However , no protein binding to isolated ISRE was induced by virus. Virus also indu ced IF-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 i s enhanced by an NF-kappa B heterodimer binding to an adjacent kappa B site . IRF-1 is not required for virus-induced IF-10 gene expression.