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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Phuangsab A, Lorence RM, Reichard KW, Peeples ME, Walter RJ . Newcastle disease virus therapy of human tumor xenografts: antitumor effects of local or systemic administration. Cancer Lett 2001; 172: 27–36.
Coffey MC, Strong JE, Forsyth PA, Lee PW . Reovirus therapy of tumors with activated Ras pathway. Science 1998; 282: 1332–1334.
Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N et al. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 2000; 6: 821–825.
Chiocca EA . Oncolytic viruses. Nat Rev Cancer 2002; 2: 938–950.
Russell SJ . RNA viruses as virotherapy agents. Cancer Gene Ther 2002; 9: 961–966.
Zeh HJ, Bartlett DL . Development of a replication-selective, oncolytic poxvirus for the treatment of human cancers. Cancer Gene Ther 2002; 9: 1001–1012.
Jacobs A, Tjuvajev JG, Dubrovin M, Akhurst T, Balatoni J, Beattie B et al. Positron emission tomography-based imaging of transgene expression mediated by replication-conditional, oncolytic herpes simplex virus type 1 mutant vectors in vivo. Cancer Res 2001; 61: 2983–2995.
Peng KW, Facteau S, Wegman T, O'Kane D, Russell SJ . Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med 2002; 8: 527–531.
Cook SH, Griffin DE . Luciferase imaging of a neurotropic viral infection in intact animals. J Virol 2003; 77: 5333–5338.
Luker GD, Bardill JP, Prior JL, Pica CM, Piwnica-Worms D, Leib DA . Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice. J Virol 2002; 76: 12149–12161.
Le LP, Le HN, Dmitriev IP, Davydova JG, Gavrikova T, Yamamoto S et al. Dynamic monitoring of oncolytic adenovirus in vivo by genetic capsid labeling. J Natl Cancer Inst 2006; 98: 203–214.
Knipe DM . The role of viral and cellular nuclear proteins in herpes simplex virus replication. Adv Virus Res 1989; 37: 85–123.
Roizman B, Whitley RJ . The nine ages of herpes simplex virus. Herpes 2001; 8: 23–27.
Roizman B . The function of herpes simplex virus genes: a primer for genetic engineering of novel vectors. Proc Natl Acad Sci USA 1996; 93: 11307–11312.
Rajcani J, Andrea V, Ingeborg R . Peculiarities of herpes simplex virus (HSV) transcription: an overview. Virus Genes 2004; 28: 293–310.
Contag PR, Olomu IN, Stevenson DK, Contag CH . Bioluminescent indicators in living mammals. Nat Med 1998; 4: 245–247.
Bhaumik S, Gambhir SS . Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci USA 2002; 99: 377–382.
Contag CH, Bachmann MH . Advances in in vivo bioluminescence imaging of gene expression. Annu Rev Biomed Eng 2002; 4: 235–260.
Shah K, Tang Y, Breakefield X, Weissleder R . Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo. Oncogene 2003; 22: 6865–6872.
Terada K, Wakimoto H, Tyminski E, Chiocca EA, Saeki Y . Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models. Gene Therapy 2006; 13: 705–714.
Ichikawa T, Hogemann D, Saeki Y, Tyminski E, Terada K, Weissleder R et al. MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia 2002; 4: 523–530.
Schang LM, Rosenberg A, Schaffer PA . Transcription of herpes simplex virus immediate-early and early genes is inhibited by roscovitine, an inhibitor specific for cellular cyclin-dependent kinases. J Virol 1999; 73: 2161–2172.
Schang LM, Rosenberg A, Schaffer PA . Roscovitine, a specific inhibitor of cellular cyclin-dependent kinases, inhibits herpes simplex virus DNA synthesis in the presence of viral early proteins. J Virol 2000; 74: 2107–2120.
Purifoy DJ, Powell KL . Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: temperature-sensitive mutants. J Virol 1977; 24: 470–477.
Ejercito PM, Kieff ED, Roizman B . Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol 1968; 2: 357–364.
Leopardi R, Roizman B . The herpes simplex virus major regulatory protein ICP4 blocks apoptosis induced by the virus or by hyperthermia. Proc Natl Acad Sci USA 1996; 93: 9583–9587.
Fu X, Meng F, Tao L, Jin A, Zhang X . A strict-late viral promoter is a strong tumor-specific promoter in the context of an oncolytic herpes simplex virus. Gene Therapy 2003; 10: 1458–1464.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gt.3302831
Keywords
This article is cited by
-
Glioblastoma infiltration of both tumor- and virus-antigen specific cytotoxic T cells correlates with experimental virotherapy responses
Scientific Reports (2020)
-
Designing herpes viruses as oncolytics
Molecular Therapy - Oncolytics (2015)
-
Multimechanistic Tumor Targeted Oncolytic Virus Overcomes Resistance in Brain Tumors
Molecular Therapy (2013)
-
Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII-bearing tumor cells
Cancer Gene Therapy (2010)
-
Non-invasive Imaging in Gene Therapy
Molecular Therapy (2007)