ArticlePLoS pathogens2018
Active-site mTOR inhibitors augment HSV1-dICP0 infection in cancer cells via dysregulated eIF4E/4E-BP axis.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
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- The 4EHP-mediated translational repression of cGAS impedes the host immune response against DNA viruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.Nature communications · 2024Article
- Regulation of stress granule formation in human oligodendrocytes.Nature communications · 2024Article
- Primate Simplexviruses Differ in Tropism for Macaque Cells.Microorganisms · 2022Article
- Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways.Molecular cancer · 2022Review
- Regulation of herpes simplex virus type 1 latency-reactivation cycle and ocular disease by cellular signaling pathways.Experimental eye research · 2022Article
- Review
- eIF6 promotes the malignant progression of human hepatocellular carcinoma via the mTOR signaling pathway.Journal of translational medicine · 2021Article
- Emerging translation strategies during virus-host interaction.Wiley interdisciplinary reviews. RNA · 2021Review
- The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment.Oncolytic virotherapy · 2021Review
- Infection by the Protozoan ParasiteFrontiers in cellular and infection microbiology · 2020Article
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Herpes Simplex Virus 1 (HSV1) is amongst the most clinically advanced oncolytic virus platforms. However, efficient and sustained viral replication within tumours is limiting. Rapamycin can stimulate HSV1 replication in cancer cells, but active-site dual mTORC1 and mTORC2 (mammalian target of rapamycin complex 1 and 2) inhibitors (asTORi) were shown to suppress the virus in normal cells. Surprisingly, using the infected cell protein 0 (ICP0)-deleted HSV1 (HSV1-dICP0), we found that asTORi markedly augment infection in cancer cells and a mouse mammary cancer xenograft. Mechanistically, asTORi repressed mRNA translation in normal cells, resulting in defective antiviral response but also inhibition of HSV1-dICP0 replication. asTORi also reduced antiviral response in cancer cells, however in contrast to normal cells, transformed cells and cells transduced to elevate the expression of eukaryotic initiation factor 4E (eIF4E) or to silence the repressors eIF4E binding proteins (4E-BPs), selectively maintained HSV1-dICP0 protein synthesis during asTORi treatment, ultimately supporting increased viral replication. Our data show that altered eIF4E/4E-BPs expression can act to promote HSV1-dICP0 infection under prolonged mTOR inhibition. Thus, pharmacoviral combination of asTORi and HSV1 can target cancer cells displaying dysregulated eIF4E/4E-BPs axis.
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