The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation
Open accessAbstract
Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that causes no currently known pathology in humans. Despite the fact that this virus is of increasing interest to molecular medicine as a vector for gene delivery, relatively little is known about the cellular mechanisms controlling infection. In this study, we have examined endocytic and intracellular trafficking of AAV-2 using fluorescent (Cy3)-conjugated viral particles and molecular techniques. Our results demonstrate that internalization of heparan sulfate proteoglycan-bound AAV-2 requires αVβ5 integrin and activation of the small GTP-binding protein Rac1. Following endocytosis, activation of a phosphatidylinositol-3 (PI3) kinase pathway was necessary to initiate intracellular movement of AAV-2 to the nucleus via both microfilaments and microtubules. Inhibition of Rac1 using a dominant N17Rac1 mutant led to a decrease in AAV-2-mediated PI3 kinase activation, indicating that Rac1 may act proximal to PI3 kinase during AAV-2 infection. In summary, our results indicate that αVβ5 integrin-mediated endocytosis of AAV-2 occurs through a Rac1 and PI3 kinase activation cascade, which directs viral movement along the cytoskeletal network to the nucleus.
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Cites
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Recombinant adeno-associated virus for muscle directed gene therapy
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“Cy3-labeled rAAV has recently become a valuable tool to analyze rAAV transduction (5, 6, 24, 51).”
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Self-citationEndosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus
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Cited by
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926
Burger, C., Gorbatyuk, O. S., Velardo, M. J., Peden, C. S., Williams, P., Zolotukhin, S., Reier, P. J., Mandel, R. J., & Muzyczka, N. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.05.024 · Cited by 741
Zhong, L., Li, B., Mah, C. S., Govindasamy, L., Agbandje-McKenna, M., Cooper, M., Herzog, R. W., Zolotukhin, I., Warrington, K. H., Weigel-Van Aken, K. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802866105 · Cited by 558
A Viral Phospholipase A2 Is Required for Parvovirus Infectivity
Zádori, Z., Szelei, J., Lacoste, M.-C., Li, Y., Gariépy, S., Raymond, P., Allaire, M., Nabi, I. R., & Tijssen, P. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00031-4 · Cited by 518
Identification of a heparin-binding motif on adeno-associated virus type 2 capsids
Kern, A., Schmidt, K., Leder, C., Müller, O. J., Wobus, C. E., Bettinger, K., Von der Lieth, C. W., King, J. A., & Kleinschmidt, J. A. (2003) · Journal of Virology · doi:10.1128/jvi.77.20.11072-11081.2003 · Cited by 380
Metadata
- Authors
- Sanlioglu, S., Benson, P. K., Yang, J., Atkinson, E. M., Reynolds, T., & Engelhardt, J. F.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2000-10
- Volume
- 74
- Issue
- 19
- Pages
- 9184-9196
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2062840171
- Cited by
- 269
- References
- 6
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Sanlioglu, S., Benson, P. K., Yang, J., Atkinson, E. M., Reynolds, T., & Engelhardt, J. F. (2000). Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation. Journal of Virology. https://doi.org/10.1128/jvi.74.19.9184-9196.2000
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