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Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and replication in tumors

Gene Therapy volume 13, pages 1731–1736 (2006)Cite this article

Abstract

An increasing number of oncolytic viruses have been developed and studied for cancer therapy. In response to needs for non-invasive monitoring and imaging of oncolytic virotherapy, several different approaches, including a positron emission tomography-based method, a method using secreted marker peptides, and optical imaging-based methods, have been reported. Among these modalities, we utilized the luciferase-based bioluminescent assay/imaging systems to determine the kinetics and dynamics of a productive viral infection. The replication cycle of herpes simplex virus type 1 (HSV-1) is punctuated by a temporal cascade of three classes of viral genes: immediate-early (IE), early (E) and late (L) genes. UL39- and γ134.5-deleted, replication-conditional HSV-1 mutants that express firefly luciferase under the control of the IE4/5 or strict-late gC promoters were generated. These oncolytic viruses were examined in cultured cells and a mouse tumor model. IE promoter- and strict-late promoter-mediated luciferase expression was confirmed to indicate viral infection and replication, respectively. Incorporation of a strict-late promoter-driven luciferase cassette into oncolytic HSV-1 vectors would be useful for assessing tumor oncolysis in preclinical tumor treatment studies.

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Acknowledgements

This project was supported by Grants P01 CA69246, R01 NS41571 and R01 CA85139 to EAC and by the Dardinger Center Fund for Neuro-oncology Research at the James Cancer Hospital, the Ohio State University Medical Center. We wish to acknowledge Ms Rosalyn Vu and Ms Suzanne Camilli for editing the manuscript and Dr Masayuki Nitta for providing the H2B-RFP construct.

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  1. S Yamamoto

    Present address: Department of Neurosurgery, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Authors and Affiliations

  1. Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, James Cancer Hospital and Solove Research Institute, The Ohio State University Medical Center, Columbus, OH, USA

    S Yamamoto, L A Deckter, K Kasai, E A Chiocca & Y Saeki

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  1. S Yamamoto
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Correspondence to Y Saeki.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Yamamoto, S., Deckter, L., Kasai, K. et al. Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and replication in tumors. Gene Ther 13, 1731–1736 (2006). https://doi.org/10.1038/sj.gt.3302831

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