ArticleJournal of virology2003
Translational compensation of a frameshift mutation affecting herpes simplex virus thymidine kinase is sufficient to permit reactivation from latency.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Lys-specific gingipain (Kgp) ofmBio · 2025Article
- From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion.Viruses · 2021Review
- Ginkgolic Acid Inhibits Herpes Simplex Virus Type 1 Skin Infection and Prevents Zosteriform Spread in Mice.Viruses · 2021Article
- Alphaherpesvirus Genomics: Past, Present and Future.Current issues in molecular biology · 2021Review
- Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution.Journal of virology · 2018Review
- Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.Journal of virology · 2017Article
- In vivo reactivation of latent herpes simplex virus 1 in mice can occur in the brain before occurring in the trigeminal ganglion.Journal of virology · 2014Article
- Tranylcypromine reduces herpes simplex virus 1 infection in mice.Antimicrobial agents and chemotherapy · 2014Article
- Common and new acyclovir resistant herpes simplex virus-1 mutants causing bilateral recurrent herpetic keratitis in an immunocompetent patient.The Journal of infectious diseases · 2014Article
- Article
- 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
- 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
- Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management.Antimicrobial agents and chemotherapy · 2011Review
- Antiviral drug resistance: mechanisms and clinical implications.Infectious disease clinics of North America · 2010Review
- A gripping tale of ribosomal frameshifting: extragenic suppressors of frameshift mutations spotlight P-site realignment.Microbiology and molecular biology reviews : MMBR · 2009Review
- 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
- Diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and Ganglia.Journal of virology · 2007Article
- Low-level expression and reversion both contribute to reactivation of herpes simplex virus drug-resistant mutants with mutations on homopolymeric sequences in thymidine kinase.Journal of virology · 2006Article
- An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Herpes simplex virus thymidine kinase is important for reactivation of virus from its latent state and is a target for the antiviral drug acyclovir. Most acyclovir-resistant isolates have mutations in the thymidine kinase gene; however, how these mutations confer clinically relevant resistance is unclear. Reactivation from explanted mouse ganglia was previously observed with a patient-derived drug-resistant isolate carrying a single guanine insertion within a run of guanines in the thymidine kinase gene. Despite this mutation, low levels of active enzyme were synthesized following an unusual ribosomal frameshift. Here we report that a virus, generated from a pretherapy isolate from the same patient, engineered to lack thymidine kinase activity, was competent for reactivation. This suggested that the clinical isolate contains alleles of other genes that permit reactivation in the absence of thymidine kinase. Therefore, to establish whether thymidine kinase synthesized via a ribosomal frameshift was sufficient for reactivation under conditions where reactivation requires this enzyme, we introduced the mutation into the well-characterized strain KOS. This mutant virus reactivated from latency, albeit less efficiently than KOS. Plaque autoradiography revealed three phenotypes of reactivating viruses: uniformly low thymidine kinase activity, mixed high and low activity, and uniformly high activity. We generated a recombinant thymidine kinase-null virus from a reactivating virus expressing uniformly low activity. This virus did not reactivate, confirming that mutations in other genes that would influence reactivation had not arisen. Therefore, in strains that require thymidine kinase for reactivation from latency, low levels of enzyme synthesized via a ribosomal frameshift can suffice.
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