ArticlePloS one2017
Human adenovirus type 5 vectors deleted of early region 1 (E1) undergo limited expression of early replicative E2 proteins and DNA replication in non-permissive cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Adenovirus vector-mediated delivery of the CRISPR-CasRx system enables gene knockdown with suppressed collateral activity.Molecular therapy. Nucleic acids · 2026Article
- Target-Based Antiviral Drug Development Against Human Respiratory Viruses.Pathogens (Basel, Switzerland) · 2026Review
- A replication-incompetent adenovirus type 55 vaccine induces broad and durable protective immunity against pathogenic adenoviruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The Pathology of Viral Infections.Advances in experimental medicine and biology · 2026Review
- Genome-replicating HC-AdV: A novel high-capacity adenoviral vector class featuring enhancedMolecular therapy. Methods & clinical development · 2025Article
- Protein-S-nitrosylation of adenovirus-5 E1A and human papillomavirus 16 E7 limits their ability to inhibit STING activity.Journal of virology · 2025Article
- Adenoviral Vector System: A Comprehensive Overview of Constructions, Therapeutic Applications and Host Responses.Journal of microbiology (Seoul, Korea) · 2024Review
- Twenty years of Gendicine® rAd-p53 cancer gene therapy: The first-in-class human cancer gene therapy in the era of personalized oncology.Genes & diseases · 2024Review
- In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D.Journal of microbiology (Seoul, Korea) · 2024Article
- The adenovirus DNA-binding protein DBP.Journal of virology · 2024Review
- Scanning the Horizon for Environmental Applications of Genetically Modified Viruses Reveals Challenges for Their Environmental Risk Assessment.International journal of molecular sciences · 2024Review
- Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication.Journal of virology · 2023Article
- Review
- Adenovirus as a Vector and Oncolytic Virus.Current issues in molecular biology · 2023Review
- Review
- Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy.Viruses · 2022Review
- Susceptibility to SARS-CoV-2 omicron following ChAdOx1 nCoV-19 and BNT162b2 versus CoronaVac vaccination.iScience · 2022Article
- Article
- SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription.Genome medicine · 2021Article
- Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies.Cancers · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenovirus (Ad) vectors deleted of the early region 1 (E1) are widely used for transgene delivery in preclinical and clinical gene therapy studies. Although proteins encoded within the E1 region are required for efficient virus replication, previous studies have suggested that certain viral or cellular proteins can functionally compensate for E1, leading to expression of the early region 2 (E2)-encoded replicative proteins and subsequent virus replication. We have generated a series of E1-encoding and E1-deficient Ad vectors containing a FLAG-epitope tag on each of the E2-encoded proteins: DNA-binding protein (DBP), terminal protein (TP) and DNA polymerase (Pol). Using these constructs, we show that for the replication-competent virus, the expression level of each E2-encoded protein declines with increasing distance from the E2 promoter, with E2A-encoded DBP expression being ~800-fold higher than E2B-encoded TP. Pol was expressed at extremely low levels in infected cells, and immunoprecipitation from cell lysates was required prior to its detection by immunoblot. We further show that DBP was expressed 200- to 400-fold less efficiently from an E1-deficient virus compared to a replication-competent virus in A549 and HepG2 cells, which was accompanied by a very small increase in genome copy number. For the E1-deficient virus, late gene expression (a marker of virus replication) was only observed at very high multiplicities of infection. These data show that E1-deleted Ad gives rise to limited expression of the E2-encoded genes and replication in infected cells, but highlight the importance of considering viral dose-dependent effects in gene therapy studies.
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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.