ArticleJournal of virology2007
Surface-exposed adeno-associated virus Vp1-NLS capsid fusion protein rescues infectivity of noninfectious wild-type Vp2/Vp3 and Vp3-only capsids but not that of fivefold pore mutant virions.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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.
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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.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
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- Nanocarrier-Based Systems for Targeted Delivery: Current Challenges and Future Directions.MedComm · 2025Review
- Protein Carrier Adeno-Associated Virus.ACS nano · 2025Article
- Structural basis for nuclear import of adeno-associated virus serotype 6 capsid protein.Journal of virology · 2025Article
- Probing recombinant AAV capsid integrity and genome release after thermal stress by mass photometry.Molecular therapy. Methods & clinical development · 2024Article
- The Expression and Function of the Small Nonstructural Proteins of Adeno-Associated Viruses (AAVs).Viruses · 2024Review
- Higher-Order Structure of Adeno-Associated Virus Serotype 8 by Hydrogen/Deuterium Exchange Mass Spectrometry.Viruses · 2024Article
- Capsid-mediated control of adeno-associated viral transcription determines host range.Cell reports · 2024Article
- Article
- Structural basis for nuclear import of bat adeno-associated virus capsid protein.The Journal of general virology · 2024Article
- Enhancement of recombinant adeno-associated virus activity by improved stoichiometry and homogeneity of capsid protein assembly.Molecular therapy. Methods & clinical development · 2023Article
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- Review
- Quantitative analysis of genome packaging in recombinant AAV vectors by charge detection mass spectrometry.Molecular therapy. Methods & clinical development · 2021Article
- Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties.Nature communications · 2020Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Over the past 2 decades, significant effort has been dedicated to the development of adeno-associated virus (AAV) as a vector for human gene therapy. However, understanding of the virus with respect to the functional domains of the capsid remains incomplete. In this study, the goal was to further examine the role of the unique Vp1 N terminus, the N terminus plus the recently identified nuclear localization signal (NLS) (J. C. Grieger, S. Snowdy, and R. J. Samulski, J. Virol 80:5199-5210, 2006), and the virion pore at the fivefold axis in infection. We generated two Vp1 fusion proteins (Vp1 and Vp1NLS) linked to the 8-kDa chemokine domain of rat fractalkine (FKN) for the purpose of surface exposure upon assembly of the virion, as previously described (K. H. Warrington, Jr., O. S. Gorbatyuk, J. K. Harrison, S. R. Opie, S. Zolotukhin, and N. Muzyczka, J. Virol 78:6595-6609, 2004). The unique Vp1 N termini were found to be exposed on the surfaces of these capsids and maintained their phospholipase A2 (PLA2) activity, as determined by native dot blot Western and PLA2 assays, respectively. Incorporation of the fusions into AAV type 2 capsids lacking a wild-type Vp1, i.e., Vp2/Vp3 and Vp3 capsid only, increased infectivity by 3- to 5-fold (Vp1FKN) and 10- to 100-fold (Vp1NLSFKN), respectively. However, the surface-exposed fusions did not restore infectivity to AAV virions containing mutations at a conserved leucine (Leu336Ala, Leu336Cys, or Leu336Trp) located at the base of the fivefold pore. EM analyses suggest that Leu336 may play a role in global structural changes to the virion directly impacting downstream conformational changes essential for infectivity and not only have local effects within the pore, as previously suggested.
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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.