ArticleJournal of virology2012
Evidence for pH-dependent protease activity in the adeno-associated virus capsid.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 78 citations in OpenAlex.
- Intracellular trafficking and nuclear compartmentalization of AAV gene delivery.Molecular therapy. Advances · 2026Article
- Distinguishing Pseudotransduction and True Transduction Enables Characterization and Bioengineering of Extracellular Vesicle-Adeno-Associated Virus Vectors.Journal of extracellular vesicles · 2026Article
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Integrin beta 1 facilitates non-enveloped hepatitis E virus cell entry through the recycling endosome.Nature communications · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases.International journal of molecular sciences · 2025Review
- Molecular basis for the different PCV2 susceptibility of T-lymphoblasts in Landrace and Piétrain pigs.Veterinary research · 2024Article
- A new perspective on the evolution and diversity of the genusVirus evolution · 2022Article
- Intracellular trafficking of adeno-associated virus (AAV) vectors: challenges and future directions.Gene therapy · 2021Review
- Functional roles of the membrane-associated AAV protein MAAP.Scientific reports · 2021Article
- Adeno-associated Virus 9 Structural Rearrangements Induced by Endosomal Trafficking pH and Glycan Attachment.Journal of virology · 2021Article
- Adeno-Associated Virus (AAV) Gene Delivery: Dissecting Molecular Interactions upon Cell Entry.Viruses · 2021Review
- AAV8 transduction capacity is reduced by prior exposure to endosome-like pH conditions.Neural regeneration research · 2021Article
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies.Scientific reports · 2021Article
- Effects of Altering HSPG Binding and Capsid Hydrophilicity on Retinal Transduction by AAV.Journal of virology · 2021Article
- Article
- Effects of Thermally Induced Configuration Changes on rAAV Genome's Enzymatic Accessibility.Molecular therapy. Methods & clinical development · 2020Article
- MASS SPECTROMETRY IN VIROLOGICAL SCIENCES.Mass spectrometry reviews · 2020Review
- Monitoring Proteolytic Activity in Real Time: A New World of Opportunities for Biosensors.Trends in biochemical sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Incubation of highly purified adeno-associated virus (AAV) capsids in vitro at pH 5.5 induced significant autocleavage of capsid proteins at several amino acid positions. No autocleavage was seen at pH 7.5. Examination of other AAV serotypes showed at least two different pH-induced cleavage patterns, suggesting that different serotypes have evolved alternative protease cleavage sites. In contrast, incubation of AAV serotypes with an external protease substrate showed that purified AAV capsid preparations have robust protease activity at neutral pH but not at pH 5.5, opposite to what is seen with capsid protein autocleavage. Several lines of evidence suggested that protease activity is inherent in AAV capsids and is not due to contaminating proteins. Control virus preparations showed no protease activity on external substrates, and filtrates of AAV virus preparations also showed no protease activity contaminating the capsids. Further, N-terminal Edman sequencing identified unique autocleavage sites in AAV1 and AAV9, and mutagenesis of amino acids adjacent to these sites eliminated cleavage. Finally, mutation of an amino acid in AAV2 (E563A) that is in a conserved pH-sensitive structural region eliminated protease activity on an external substrate but did not seem to affect autocleavage. Taken together, our data suggested that AAV capsids have one or more protease active sites that are sensitive to pH induction. Further, it appears that acidic pHs comparable to those seen in late endosomes induce a structural change in the capsid that induces autolytic protease activity. The pH-dependent protease activity may have a role in viral 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.