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A novel anticancer agent ARC antagonizes HIV-1 and HCV

Oncogene volume 26, pages 3899–3903 (2007)Cite this article

Abstract

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public health concerns worldwide. HCV is clearly associated with the occurrence of hepatocellular carcinoma, and recently HIV infection has also been linked to the development of a multitude of cancers. Previously, we identified a novel nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-β-D-ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that exhibited proapoptotic and antiangiogenic properties in vitro. Here, we evaluated the effect of ARC on HIV-1 transcription and HCV replication. Using reporter assays, we found that ARC inhibited HIV-1 Tat-based transactivation in different cell systems. Also, using hepatoma cells that harbor subgenomic and full-length replicons of HCV, we found that ARC inhibited HCV replication. Together, our data indicate that ARC could be a promising candidate for the development of antiviral therapeutics against HIV and HCV.

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Acknowledgements

We thank Dr Charles Rice (Rockefeller University, NY, USA) for providing the hepatoma cell lines with the subgenomic and the full-length replicons of HCV. This work was supported by the 2006 Penny Severns award from IDPH (to ALG), start-up funds from the UIC Department of Medicine (to ALG), NIH Research Grant UH1HL 03679 funded by the National Heart, Lung, and Blood Institute and The Office of Research on Minority Health (to SN) and by NIH Grant R21 AI 156973-01 (to SN). We thank Dr Patricio Ray (Children's National Medical Center, Washington, DC, USA) for the gift of Adeno-Tat and Dr Michael Schneider (Baylor College of Medicine, TX, USA) for the gift of Adeno-dnCDK9.

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Authors and Affiliations

  1. Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, USA

    S Nekhai, T Ammosova, X Niu & A Foster

  2. Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC, USA

    S Nekhai

  3. Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    U G Bhat, S K Radhakrishnan, T J Layden & A L Gartel

  4. Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, USA

    S K Radhakrishnan & A L Gartel

  5. Children's National Medical Center, CRI Center, Washington, DC, USA

    M Jerebtsova

  6. Department of Microbiology, Howard University College of Medicine, Washington, DC, USA

    A Foster

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  1. S Nekhai
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  2. U G Bhat
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  3. T Ammosova
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Correspondence to S Nekhai or A L Gartel.

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Nekhai, S., Bhat, U., Ammosova, T. et al. A novel anticancer agent ARC antagonizes HIV-1 and HCV. Oncogene 26, 3899–3903 (2007). https://doi.org/10.1038/sj.onc.1210158

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  • DOI: https://doi.org/10.1038/sj.onc.1210158

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