Oncolytic Viruses Derived from the γ34.5-Deleted Herpes Simplex Virus Recombinant R3616 Encode a Truncated UL3 Protein
| Autor: | Natalia Martin, Nancy S. Markovitz, Jordan Trecki, Megan J. Dambach |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Gene Expression Regulation
Viral Keratinocytes Genes Viral Viral protein viruses Genetic enhancement Molecular Sequence Data Nonsense mutation Mutant DNA Recombinant Herpesvirus 1 Human Biology medicine.disease_cause Genome Viral Proteins Chlorocebus aethiops Consensus Sequence Drug Discovery Genetics medicine Animals Humans Amino Acid Sequence Vero Cells Molecular Biology Gene Pharmacology Base Sequence Sequence Homology Amino Acid Sequence Analysis DNA Virology Oncolytic virus Oncolytic Viruses Herpes simplex virus Codon Nonsense DNA Viral Molecular Medicine Rabbits Gene Deletion |
| Zdroj: | Molecular Therapy. 13:891-898 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2006.02.006 |
| Popis: | Replication-competent herpes simplex virus (HSV-1) mutants are used in clinical trials in the experimental treatment of cancer. Mutants G207, HSV1716, NV1020, and Oncovex GM-CSF share in common a defect in one or both copies of the gene encoding the neurovirulence factor, ICP34.5, and are thus neuroattenuated. These viruses are acknowledged to differ from one another (a) in the specific types of mutations intentionally introduced during their derivation and (b) in the inherent genetic differences retained from the different parent strains used in their construction. Unintended mutations are expected to emerge at some low frequency during the selection for and passage of mutant viruses. Here we demonstrate that during the construction of the oncolytic virus R3616, a nonsense mutation arose in an untargeted region of the HSV-1 genome that resulted in a substantial truncation of the viral protein known as UL3. This report is the first published documentation that oncolytic herpesviruses developed and used in clinical trials contain adventitious mutations. The implications of these findings for the characterization and development of vectors proposed for use in clinical trials are discussed. |
| Databáze: | OpenAIRE |
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