ArticleJournal of virology2009
Adenovirus activates complement by distinctly different mechanisms in vitro and in vivo: indirect complement activation by virions in vivo.
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 55 papers.
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Who cites it
55 citing papers in PubMed.
- Immune shielding of viral vectors via capsid engineering with genetically encoded zwitterionic peptides.Molecular therapy. Advances · 2026Article
- Duration of immunity following infection with moderately virulent ASFV.PLoS pathogens · 2026Article
- Bio-Compatibility Analysis of Newly Developed Plug and Cuff Electrodes for Future Neuronal Interface Applications.Biomimetics (Basel, Switzerland) · 2026Article
- Thrombotic microangiopathy following gene therapy for 5q-spinal muscular atrophy.Gene therapy · 2025Article
- Integrative Mechanistic Studies Identify Reticulon-3 as a Critical Modulator of Infectious Exosome-Driven Dengue Pathogenesis.Viruses · 2025Article
- Review
- Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.Nature communications · 2024Article
- Thrombotic Microangiopathy as an Emerging Complication of Viral Vector-Based Gene Therapy.Kidney international reports · 2024Review
- Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.Journal of medical virology · 2024Article
- Review
- Thrombotic microangiopathy following systemic AAV administration is dependent on anti-capsid antibodies.The Journal of clinical investigation · 2024Article
- Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy.Viruses · 2022Review
- Innate immune surveillance of the circulation: A review on the removal of circulating virions from the bloodstream.PLoS pathogens · 2022Review
- Cytokine Responses to Adenovirus and Adenovirus Vectors.Viruses · 2022Review
- Nonhuman Adenoviral Vector-Based Platforms and Their Utility in Designing Next Generation of Vaccines for Infectious Diseases.Viruses · 2021Review
- Genetic and Chemical Capsid Modifications of Adenovirus Vectors to Modulate Vector-Host Interactions.Viruses · 2021Review
- Risk Factors for the Development of Hemophagocytic Lymphohistiocytosis in Children With Severe Adenovirus Pneumonia: A Single-Center Retrospective Study.Frontiers in pediatrics · 2021Article
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- Innate immunity to adenovirus: lessons from mice.FEBS letters · 2019Review
- Human adenovirus type 7 infection causes a more severe disease than type 3.BMC infectious diseases · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding innate immunity is key to improving the safety of adenovirus (Ad) vectors for systemic gene therapy. Ad has been shown to activate complement in vitro, but activation of complement after Ad injection in vivo has not been directly measured. Using complement protein C3a as a marker of complement activation, we show that types 2 and 5 human Ads cause rapid complement activation after intravenous injection in mice. Unexpectedly, the mechanisms in vivo were different than those in vitro. Antibodies were critical for the activation of complement by Ad in vitro, but antibodies were not required in vivo. The classical pathway was required in vitro, whereas complement activation in vivo involved both classical and nonclassical pathways as well as the reticuloendothelial system. Remarkably, the entry-deficient Ad mutant ts1 was completely unable to activate complement in vivo even though it was fully able to activate complement in vitro. This result demonstrates that the complement system senses intravenously injected Ad primarily by detecting the effects of Ad on cells rather than through direct interaction of complement with virions. Encouragingly, shielding Ad with polyethylene glycol was effective at reducing complement activation both in vitro and in vivo. In summary, intravenously injected Ad rapidly activates complement through multiple pathways, but these pathways are different than those identified by in vitro studies. In vitro studies are poorly predictive of in vivo mechanisms because Ad virions activate complement through indirect mechanisms in vivo.
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