IP-10 gene transcription by virus in astrocytes requires cooperation of ISRE with adjacent kappaB site but not IRF-1 or viral transcription.
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.
Cheng
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G
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA.
Nazar
A S
AS
Shin
H S
HS
Vanguri
P
P
Shin
M L
ML
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D001483:Base Sequence; D002460:Cell Line; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D009522:Newcastle disease virus / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018108:Respirovirus / Q000235:genetics; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016328:NF-kappa B; D012367:RNA, Viral; D014157:Transcription Factors; D007371:Interferon-gamma