ArticleProceedings of the National Academy of Sciences of the United States of America2005
An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Discovery of functional factorless internal ribosome entry site-like structures through virome mining.PLoS pathogens · 2025Article
- Review
- Host targeted antiviral (HTA): functional inhibitor compounds of scaffold protein RACK1 inhibit herpes simplex virus proliferation.Oncotarget · 2019Article
- Long-read sequencing uncovers a complex transcriptome topology in varicella zoster virus.BMC genomics · 2018Article
- Transcriptome Analysis of the Spodoptera frugiperda AscovirusJournal of virology · 2017Article
- Structural domains within the HIV-1 mRNA and the ribosomal protein S25 influence cap-independent translation initiation.The FEBS journal · 2016Article
- Review
- The DNA virus white spot syndrome virus uses an internal ribosome entry site for translation of the highly expressed nonstructural protein ICP35.Journal of virology · 2013Article
- Tinkering with translation: protein synthesis in virus-infected cells.Cold Spring Harbor perspectives in biology · 2013Review
- Transcription of gD and gI genes in BHV1-infected cells.Journal of biosciences · 2012Article
- Net -1 frameshifting on a noncanonical sequence in a herpes simplex virus drug-resistant mutant is stimulated by nonstop mRNA.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Quantification and analysis of thymidine kinase expression from acyclovir-resistant G-string insertion and deletion mutants in herpes simplex virus-infected cells.Journal of virology · 2012Article
- IRES-Dependent Translational Control during Virus-Induced Endoplasmic Reticulum Stress and Apoptosis.Frontiers in microbiology · 2012Article
- Slipping and sliding: frameshift mutations in herpes simplex virus thymidine kinase and drug-resistance.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2011Review
- Animal virus schemes for translation dominance.Current opinion in virology · 2011Review
- Viral subversion of the host protein synthesis machinery.Nature reviews. Microbiology · 2011Review
- Identification of an intercistronic internal ribosome entry site in a Marek's disease virus immediate-early gene.Journal of virology · 2009Article
- Quantitative analysis of clinically relevant mutations occurring in lymphoid cells harboring gamma-retrovirus-encoded hsvtk suicide genes.Gene therapy · 2008Article
- Expression of extremely low levels of thymidine kinase from an acyclovir-resistant herpes simplex virus mutant supports reactivation from latently infected mouse trigeminal ganglia.Journal of virology · 2007Article
- Searching for IRES.RNA (New York, N.Y.) · 2006Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have investigated a herpes simplex virus mutant that expresses low levels of thymidine kinase (TK), a phenotype associated with drug resistance and pathogenicity, despite a single-base deletion in the gene. Using a dual-reporter system, a 39-nt sequence including the mutation was shown to direct expression of the downstream reporter gene in reticulocyte lysate. Translation of the downstream reporter was not impaired when the mRNA lacked a 5' cap or had a stable stem loop 5' of the upstream reporter and was relatively resistant to edeine, an antibiotic that prevents AUG codon recognition by the 40S-eIF2-GTP/Met-tRNAi complex. Twelve nucleotides were as active as the original sequence for translation of the downstream reporter. Surprisingly, this sequence lacks an AUG codon. Analysis of point mutations showed that a CUG codon in the sequence was important. However, many single-base changes had only limited effects, and introduction of AUG codons did not increase translation. A mutant virus containing both the single-base deletion and a mutation that reduced downstream translation in vitro had significantly less TK activity than a virus with the single-base deletion alone. Thus, a remarkably short internal ribosome entry site (IRES) that lacks an AUG codon resides in the viral tk gene. The IRES appears to be responsible for TK expression from a drug-resistant mutant that would otherwise express no TK, which may contribute to pathogenicity. Because we found numerous short sequences with IRES activity, there might be many hitherto unrecognized polypeptides expressed at low levels from eukaryotic mRNAs.
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