ArticlePLoS pathogens2016
E2F/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 78 citations in OpenAlex.
- Highly neutralizing anti-IFN-ω autoantibodies underlie severe pediatric adenovirus infection.Journal of human immunity · 2026Article
- One virus-many strategies: type-specific interactions between human adenoviruses and innate immunity.Journal of virology · 2026Review
- Integration of a multimeric STAT consensus site into the adenoviral genome to interfere with IFN signaling represents a novel concept to improve oncolytic virotherapy.Journal of virology · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Transcriptional transactivation turns human iPSC-derived macrophages into an adenovirus-producing cell state.Journal of virology · 2026Article
- Oncolytic adenovirus armed with cGAS activates STING pathway and enhances antitumor immunity in lung cancer with superior combined efficacy of PD-L1 therapy.Frontiers in immunology · 2026Article
- Genome-replicating HC-AdV: A novel high-capacity adenoviral vector class featuring enhancedMolecular therapy. Methods & clinical development · 2025Article
- Cellular transcription factor TFII-I represses adenovirus gene expression.Journal of virology · 2025Article
- Activated blood-derived human primary T cells support replication of HAdV C5 and virus transmission to polarized human primary epithelial cells.Journal of virology · 2025Article
- Evaluation of Lytic and Persistent Human Adenovirus Infections in Tonsil Tissue of Children With Tonsillar Hypertrophy: A Matched Case-Control Study.Laryngoscope investigative otolaryngology · 2025Article
- Three modes of viral adaption by the heart.Science advances · 2024Article
- Article
- Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures.EBioMedicine · 2024Article
- Review
- Three Modes of Viral Adaption by the Heart.bioRxiv : the preprint server for biology · 2024Article
- Oncolytic Viruses in the Era of Omics, Computational Technologies, and Modeling: Thesis, Antithesis, and Synthesis.International journal of molecular sciences · 2023Review
- Pathogenicity and virulence of human adenovirus F41: Possible links to severe hepatitis in children.Virulence · 2023Review
- Adenoviruses in medicine: innocuous pathogen, predator, or partner.Trends in molecular medicine · 2023Review
- Interferon alpha and beta receptor 1 knockout in human embryonic kidney 293 cells enhances the production efficiency of proteins or adenoviral vectors related to type I interferons.Frontiers in bioengineering and biotechnology · 2023Article
- Gastrointestinal organoids in the study of viral infections.American journal of physiology. Gastrointestinal and liver physiology · 2023Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Interferons (IFNs) are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity. IFNs have broad antiviral properties and function by different mechanisms. IFNs fail to inhibit wild-type Adenovirus (Ad) replication in established cancer cell lines. In this study, we analyzed the effects of IFNs on Ad replication in normal human cells. Our data demonstrate that both IFNα and IFNγ blocked wild-type Ad5 replication in primary human bronchial epithelial cells (NHBEC) and TERT-immortalized normal human diploid fibroblasts (HDF-TERT). IFNs inhibited the replication of divergent adenoviruses. The inhibition of Ad5 replication by IFNα and IFNγ is the consequence of repression of transcription of the E1A immediate early gene product. Both IFNα and IFNγ impede the association of the transactivator GABP with the E1A enhancer region during the early phase of infection. The repression of E1A expression by IFNs requires a conserved E2F binding site in the E1A enhancer, and IFNs increased the enrichment of the E2F-associated pocket proteins, Rb and p107, at the E1A enhancer in vivo. PD0332991 (Pabociclib), a specific CDK4/6 inhibitor, dephosphoryles pocket proteins to promote their interaction with E2Fs and inhibited wild-type Ad5 replication dependent on the conserved E2F binding site. Consistent with this result, expression of the small E1A oncoprotein, which abrogates E2F/pocket protein interactions, rescued Ad replication in the presence of IFNα or IFNγ. Finally, we established a persistent Ad infection model in vitro and demonstrated that IFNγ suppresses productive Ad replication in a manner dependent on the E2F binding site in the E1A enhancer. This is the first study that probes the molecular basis of persistent adenovirus infection and reveals a novel mechanism by which adenoviruses utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.
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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.