ArticleJournal of virology2009
Activation of the PI3K/Akt pathway early during vaccinia and cowpox virus infections is required for both host survival and viral replication.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 132 citations in OpenAlex.
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
- Loss of Akt3 enhances antiviral immunity while disrupting corneal homeostasis during ocular HSV-1 infection.Frontiers in immunology · 2026Article
- Viral insulin/IGF-like peptides inhibit IGF-1 receptor signaling to enhance viral replication.Cell reports · 2025Article
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- Exploring the function and pathogenicity of Goatpox virus N1L gene using recombinant vaccinia virus Tiantan strain.Frontiers in veterinary science · 2025Article
- Inositol metabolism as a broad-spectrum antiviral target.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
- Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection.Journal of virology · 2024Article
- Multi-omics characterization of the monkeypox virus infection.Nature communications · 2024Article
- Vaccinia Virus Defective Particles Lacking the F17 Protein Do Not Inhibit Protein Synthesis: F17, a Double-Edged Sword for Protein Synthesis?International journal of molecular sciences · 2024Article
- Neutrophils in oncolytic virus immunotherapy.Frontiers in immunology · 2024Review
- Evaluation of the Antiviral Activity of Tabamide A and Its Structural Derivatives against Influenza Virus.International journal of molecular sciences · 2023Article
- Cargo-Dependent Targeted Cellular Uptake Using Quaternized Starch as a Carrier.Nanomaterials (Basel, Switzerland) · 2023Article
- Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins.bioRxiv : the preprint server for biology · 2023Article
- Human monkeypox infection threat: A comprehensive overview.PLoS neglected tropical diseases · 2023Review
- Effects of Oncolytic Vaccinia Viruses Harboring Different Marine Lectins on Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2023Article
- A Comparative Study of Oncolytic Vaccinia Viruses Harboring Different Marine Lectins in Breast Cancer Cells.Marine drugs · 2023Article
- PI3K/Akt/Nrf2 mediated cellular signaling and virus-host interactions: latest updates on the potential therapeutic management of SARS-CoV-2 infection.Frontiers in molecular biosciences · 2023Review
- Live and let die: signaling AKTivation and UPRegulation dynamics in SARS-CoVs infection and cancer.Cell death & disease · 2022Review
- Ribosomes in poxvirus infection.Current opinion in virology · 2022Review
17 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
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral manipulation of the transduction pathways associated with key cellular functions such as actin remodeling, microtubule stabilization, and survival may favor a productive viral infection. Here we show that consistent with the vaccinia virus (VACV) and cowpox virus (CPXV) requirement for cytoskeleton alterations early during the infection cycle, PBK/Akt was phosphorylated at S473 [Akt(S473-P)], a modification associated with the mammalian target of rapamycin complex 2 (mTORC2), which was paralleled by phosphorylation at T308 [Akt(T308-P)] by PI3K/PDK1, which is required for host survival. Notably, while VACV stimulated Akt(S473-P/T308-P) at early (1 h postinfection [p.i.]) and late (24 h p.i.) times during the infective cycle, CPXV stimulated Akt at early times only. Pharmacological and genetic inhibition of PI3K (LY294002) or Akt (Akt-X and a dominant-negative form of Akt-K179M) resulted in a significant decline in virus yield (from 80% to >/=90%). This decline was secondary to the inhibition of late viral gene expression, which in turn led to an arrest of virion morphogenesis at the immature-virion stage of the viral growth cycle. Furthermore, the cleavage of both caspase-3 and poly(ADP-ribose) polymerase and terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labeling assays confirmed that permissive, spontaneously immortalized cells such as A31 cells and mouse embryonic fibroblasts (MEFs) underwent apoptosis upon orthopoxvirus infection plus LY294002 treatment. Thus, in A31 cells and MEFs, early viral receptor-mediated signals transmitted via the PI3K/Akt pathway are required and precede the expression of viral antiapoptotic genes. Additionally, the inhibition of these signals resulted in the apoptosis of the infected cells and a significant decline in viral titers.
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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.