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Mediators Inflamm. 2015;2015:495370. doi: 10.1155/2015/495370. Epub 2015 May 5.

Activation of CXCL-8 Transcription by Hepatitis E Virus ORF-1 via AP-1.

Author information

1
VIDO-InterVac, Vaccinology and Immunotherapeutics Program, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.
2
VIDO-InterVac, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3 ; Henan Agricultural University, 95 Wenhua Road, Zhengzhou, Henan 450002, China.
3
VIDO-InterVac, Vaccinology and Immunotherapeutics Program, Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.

Abstract

Hepatitis E virus (HEV) is a small nonenveloped single-stranded positive-sense RNA virus and is one of the major causes for acute hepatitis worldwide. CXCL-8 is a small multifunctional proinflammatory chemokine. It was reported recently that HEV infection significantly upregulates CXCL-8 gene expression. In this study, we investigated the mechanism of HEV-induced CXCL-8 transcriptional activation. Using CXCL-8 promoter reporters of different lengths ranging from -1400 to -173, we showed that -173 promoter has the highest promoter activity in the presence of HEV genomic RNA, indicating that the -173 promoter contains sequences responsible for CXCL-8 activation by HEV. Ectopic expression of the ORF-1 protein can upregulate the -173 CXCL-8 promoter activity. In contrast, expression of the ORF-2 protein suppresses the CXCL-8 promoter activity and expression of the ORF-3 protein has no effect on the CXCL-8 promoter activity. We further showed that AP-1 is required for CXCL-8 activation because neither HEV genomic RNA nor the ORF-1 protein can upregulate the -173 CXCL-8 promoter in the absence of the AP-1 binding sequence. Taken together, our results showed that HEV and HEV ORF-1 protein activate the CXCL-8 promoter via AP-1. This novel function of HEV ORF-1 protein should contribute to our understanding of HEV-host interactions and HEV-associated pathogenesis.

PMID:
26074679
PMCID:
PMC4436455
DOI:
10.1155/2015/495370
[Indexed for MEDLINE]
Free PMC Article

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