ArticleJournal of virology2012
Effect of γ34.5 deletions on oncolytic herpes simplex virus activity in brain tumors.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 105 citations in OpenAlex.
- Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.ImmunoTargets and therapy · 2026Review
- Retargeted oncolytic viruses engineered to remodel the tumor microenvironment for glioblastoma immunotherapy.Nature cancer · 2025Article
- Antiviral responses in peripheral and brain neurons.Current opinion in immunology · 2025Review
- Oncolytic HSV-1 expressing GM-CSF and IL-12 enhances anti-tumor efficacy in immunocompetent murine melanoma model.Virologica Sinica · 2025Article
- A comprehensive review redefining viruses as therapeutic agents in cancer treatment.Discover oncology · 2025Review
- Review
- Review
- Oncolytic virus-mediated immunomodulation in glioblastoma: Insights from clinical trials and challenges.Seminars in immunology · 2025Review
- Antibiotic-mediated selection of randomly mutagenized and cytokine-expressing oncolytic viruses.Nature biomedical engineering · 2025Article
- Advances in the Drug Development and Quality Evaluation Principles of Oncolytic Herpes Simplex Virus.Viruses · 2025Review
- Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Harnessing Oncolytic Viruses for Targeted Therapy in Triple-Negative Breast Cancer.International journal of medical sciences · 2025Review
- Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy.Cancers · 2024Review
- Review
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- Emerging Therapies for Glioblastoma.Cancers · 2024Review
- Advanced progress in the genetic modification of the oncolytic HSV-1 virus.Frontiers in oncology · 2024Review
- Article
- Review
- Oncolytic herpes simplex virus armed with a bacterial GBP1 degrader improves antitumor activity.Molecular therapy oncolytics · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The ICP34.5 protein of herpes simplex virus (HSV) is involved in many aspects of viral pathogenesis; promoting neurovirulence, inhibiting interferon-induced shutoff of protein synthesis, interacting with PCNA and TBK1, inhibiting dendritic cell (DC) maturation, and binding to Beclin 1 to interfere with autophagy. Because of its key role in neuropathogenicity, the γ34.5 gene is deleted in all oncolytic HSVs (oHSVs) currently in clinical trial for treating malignant gliomas. Unfortunately, deletion of γ34.5 attenuates virus replication in cancer cells, especially human glioblastoma stem cells (GSCs). To develop new oHSVs for use in the brain and that replicate in GSCs, we explored the effect of deleting the γ34.5 Beclin 1 binding domain (BBD). To ensure cancer selectivity and safety, we inactivated the ICP6 gene (UL39, large subunit of ribonucleotide reductase), constructing ICP6 mutants with different γ34.5 genotypes: Δ68HR-6, intact γ34.5; Δ68H-6, γ34.5 BBD deleted; and 1716-6, γ34.5 deleted. Multimutated Δ68H-6 exhibited minimal neuropathogenicity in HSV-1-susceptible mice, as opposed to Δ68H and Δ68HR-6. It replicated well in human glioma cell lines and GSCs, effectively killing cells in vitro and prolonging survival of mice bearing orthotopic brain tumors. In contrast, 1716 and 1716-6 barely replicated in GSCs. Infection of glioma cells with Δ68H-6 and 1716-6 induced autophagy and increased phosphorylation of eIF2α, while inhibition of autophagy, by Beclin 1 short hairpin RNA (shRNA) knockdown or pharmacological inhibition, had no effect on virus replication or phosphorylated eIF2α (p-eIF2α) levels. Thus, Δ68H-6 represents a new oHSV vector that is safe and effective against a variety of brain tumor models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.