Imaging immediate-early and strict-late promoter activity during oncolytic herpes simplex virus type 1 infection and replication in tumors.
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. U(L)39- and gamma(1)34.5-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.
Yamamoto
S
S
Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Cancer Hospital and Solove Research Institute, The Ohio State University Medical Center, Columbus, OH, USA.
Deckter
L A
LA
Kasai
K
K
Chiocca
E A
EA
Saeki
Y
Y
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression / Q000187:drug effects; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006561:Herpes Simplex / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D009374:Neoplasms, Experimental / Q000628:therapy* / Q000821:virology; D009457:Neuroglia / Q000201:enzymology; D050130:Oncolytic Virotherapy / Q000379:methods*; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011687:Purines / Q000494:pharmacology; D000077546:Roscovitine; D014709:Vero Cells; D014779:Virus Replication
D000998:Antiviral Agents; D008164:Luminescent Proteins; D011687:Purines; D000077546:Roscovitine; D008156:Luciferases; D010746:Phosphonoacetic Acid