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Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-κB

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Summary

Hepatitis C is a devastating disease worldwide. Proteins encoded by the etiologic agent, hepatitis C virus (HCV), are believed to play important roles in HCV-associated pathogenesis. However, the biological functions of the non-structural protein-2 (NS2) encoded by HCV are not well characterized. Here, we show that HCV NS2 protein activates CXCL-8 (interleukin-8, IL-8) transcription in HepG2 cells as measured by reverse transcription-polymerase chain reaction and IL-8 promoter-luciferase reporter assays. Furthermore, when the κB site on the IL-8 promoter was eliminated by mutagenesis or when intracellular NF-κB activity was suppressed by an inhibitor, NS2 did not activate the IL-8 promoter, suggesting a role of NF-κB in this process. These results prompted us to hypothesize that HCV NS2 might be able to activate NF-κB. This hypothesis was tested by determination of NF-κB-driven reporter gene expression and NF-κB p65 subunit subcellular localization after HCV NS2 expression. Indeed, NS2 could up-regulate NF-κB-driven luciferase activity and was associated with p65 nuclear localization. These results demonstrate that HCV NS2 up-regulates IL-8 transcription through NF-κB. This newly identified function increases our understanding of the role of HCV NS2 protein in virus-host interactions.

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Authors and Affiliations

  1. Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada

    J.-K. Oem, C. Jackel-Cram, Y.-P. Li, H.-N. Kang, Y. Zhou, L. A. Babiuk & Q. Liu

  2. University of Alberta, Edmonton, AB, Canada

    L. A. Babiuk

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  1. J.-K. Oem
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  2. C. Jackel-Cram
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  3. Y.-P. Li
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  4. H.-N. Kang
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  5. Y. Zhou
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  6. L. A. Babiuk
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  7. Q. Liu
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Correspondence to Q. Liu.

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Present address: Y.-P. Li, National Veterinary Institute, Technical University of Denmark, Hangøvej, Århus N, Denmark

Present address: H.-N. Kang, Korea Food and Drug Administration, Seoul, South Korea

Correspondence: Qiang Liu, Ph.D., Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3 Canada

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Oem, JK., Jackel-Cram, C., Li, YP. et al. Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-κB. Arch Virol 153, 293–301 (2008). https://doi.org/10.1007/s00705-007-1103-1

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  • DOI: https://doi.org/10.1007/s00705-007-1103-1

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