ArticleGenes & development2010
Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 140 citations in OpenAlex.
- Overcoming IGF1R-mediated resistance to oncolytic HSV1 and radiotherapy via triple combination therapy.Cell death & disease · 2026Article
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- SGK2 mediates apoptosis in herpes simplex keratitis by suppressing protective autophagy via the mTOR pathway.Virology journal · 2026Article
- Overcoming IGF1R-Mediated Resistance to Oncolytic HSV1 and Radiotherapy via Triple Combination Therapy.Research square · 2025Article
- HSV-1 US3: A Master Mimic Hijacking Host Kinase Networks for Viral Dominance.Journal of medical virology · 2025Review
- Phosphatase PP2A promotes RTA dephosphorylation to impair KSHV lytic replication.PLoS pathogens · 2025Article
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Impact of the changes in substrate specificity of herpes simplex virus 1 protein kinase Us3 on viral infectionJournal of virology · 2025Article
- Polyclonal LC3B Antibodies Generate Non-Specific Staining in the Nucleus of Herpes Simplex Virus Type 1-Infected Cells: Caution in the Interpretation of LC3 Staining in the Immunofluorescence Analysis of Viral Infections.International journal of molecular sciences · 2025Article
- Post-translational modifications as a key mechanism for herpes simplex virus type I evasion of host innate immunity.Frontiers in microbiology · 2025Review
- Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice.PLoS pathogens · 2024Article
- Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus-mediated disruption of the nonclassical MHC class I-related molecule MR1.The Journal of biological chemistry · 2024Article
- Viral MicroRNAs in Herpes Simplex Virus 1 Pathobiology.Current pharmaceutical design · 2024Review
- GARP and EARP are required for efficient BoHV-1 replication as identified by a genome wide CRISPR knockout screen.PLoS pathogens · 2023Article
- Cellular state landscape and herpes simplex virus type 1 infection progression are connected.Nature communications · 2023Article
- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Modifications of the PI3K/Akt/mTOR axis during FeHV-1 infection in permissive cells.Frontiers in veterinary science · 2023Article
- Interplay between Autophagy and Herpes Simplex Virus Type 1: ICP34.5, One of the Main Actors.International journal of molecular sciences · 2022Review
- Article
- An eIF3d-dependent switch regulates HCMV replication by remodeling the infected cell translation landscape to mimic chronic ER stress.Cell reports · 2022Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
All viruses require cellular ribosomes to translate their mRNAs. Viruses producing methyl-7 (m⁷) GTP-capped mRNAs, like Herpes Simplex Virus-1 (HSV-1), stimulate cap-dependent translation by activating mTORC1 to inhibit the translational repressor 4E-binding protein 1 (4E-BP1). Here, we establish that the HSV-1 kinase Us3 masquerades as Akt to activate mTORC1. Remarkably, Us3 displays no sequence homology with the cellular kinase Akt, yet directly phosphorylates tuberous sclerosis complex 2 (TSC2) on the same sites as Akt. TSC2 depletion rescued Us3-deficient virus replication, establishing that Us3 enhances replication by phosphorylating TSC2 to constitutively activate mTORC1, effectively bypassing S6K-mediated feedback inhibition. Moreover, Us3 stimulated Akt substrate phosphorylation in infected cells, including FOXO1 and GSK3. Thus, HSV-1 encodes an Akt surrogate with overlapping substrate specificity to activate mTORC1, stimulating translation and virus replication. This establishes Us3 as a unique viral kinase with promising drug development potential.
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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.