1887

Abstract

The helper-dependent adeno-associated viruses (AAVs) have attracted great interest as vectors for gene therapy. Uptake and intracellular trafficking pathways of AAV are of importance, since they are often rate-limiting steps in infection. Here, we have investigated the entry of AAV type 5 (AAV5) in primary human embryo fibroblasts. At low binding temperatures, numerous virions are concentrated between cells, at contact points between cells and cellular protrusions, and at filopodia. When the temperature is raised to 37 °C, uptake of AAV5 takes place but up to 80 % of the bound virions dissociate from the cells. Uptake is achieved by cellular structures that are part of at least two different entry pathways. In addition to the common clathrin-dependent route, caveolar endocytosis and caveosome-like organelles are involved in a second pathway not yet described for parvoviruses. Both pathways can be used in parallel to enter an individual cell.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.005595-0
2009-02-01
2019-11-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/90/2/317.html?itemId=/content/journal/jgv/10.1099/vir.0.005595-0&mimeType=html&fmt=ahah

References

  1. Bantel-Schaal, U. ( 1999; ). Chromosomal integration of adeno-associated parvovirus DNA limits proliferation and dispersal of human MKr melanoma cells in co-cultures with human fibroblasts. Cancer Lett 147, 45–53.[CrossRef]
    [Google Scholar]
  2. Bantel-Schaal, U. & Stöhr, M. ( 1992; ). Influence of adeno-associated virus on adherence and growth properties of normal cells. J Virol 66, 773–779.
    [Google Scholar]
  3. Bantel-Schaal, U. & zur Hausen, H. ( 1984; ). Characterization of the DNA of a defective parvovirus isolated from a genital site. Virology 134, 52–63.[CrossRef]
    [Google Scholar]
  4. Bantel-Schaal, U. & zur Hausen, H. ( 1988; ). Adeno-associated virus inhibit SV40 DNA amplification and replication of herpes simplex virus in SV40-transformed hamster cells. Virology 164, 64–74.[CrossRef]
    [Google Scholar]
  5. Bantel-Schaal, U., Delius, H., Schmidt, R. & zur Hausen, H. ( 1999; ). Human adeno-associated virus type 5 is only distantly related to other known primate helper-dependent parvoviruses. J Virol 73, 939–947.
    [Google Scholar]
  6. Bantel-Schaal, U., Hub, B. & Kartenbeck, J. ( 2002; ). Endocytosis of adeno-associated virus type 5 leads to accumulation of virus particles in the Golgi compartment. J Virol 76, 2340–2349.[CrossRef]
    [Google Scholar]
  7. Bartlett, J. S., Wilcher, R. & Samulski, R. J. ( 2000; ). Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol 74, 2777–2785.[CrossRef]
    [Google Scholar]
  8. Berns, K. & Parrish, C. R. ( 2007; ). Parvoviridae. In Fields Virology, 5th edn, pp. 2437–2478. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  9. Chiorini, J. A., Kim, F., Yang, L. & Kotin, R. ( 1999; ). Cloning and characterization of adeno-associated virus type 5. J Virol 73, 1309–1319.
    [Google Scholar]
  10. Ding, W., Zhang, L., Yan, Z. & Engelhardt, J. F. ( 2005; ). Intracellular trafficking of adeno-associated viral vectors. Gene Ther 12, 873–880.[CrossRef]
    [Google Scholar]
  11. Ding, W., Zhang, L. N., Yeaman, C. & Engelhardt, J. F. ( 2006; ). rAAV2 traffics through both the late and the recycling endosomes in a dose-dependent fashion. Mol Ther 13, 671–682.[CrossRef]
    [Google Scholar]
  12. Di Pasquale, G., Davidson, B. L., Stein, C. S., Martins, I., Scudiero, D., Monks, A. & Chiorini, J. A. ( 2003; ). Identification of PDGFR as a receptor for AAV-5 transduction. Nat Med 9, 1306–1312.[CrossRef]
    [Google Scholar]
  13. Faix, J. & Rottner, K. ( 2006; ). The making of filopodia. Curr Opin Cell Biol 18, 18–25.[CrossRef]
    [Google Scholar]
  14. Gao, G., Vandenberghe, L. H. & Wilson, J. M. ( 2005; ). New recombinant serotypes of AAV vectors. Curr Gene Ther 5, 285–297.[CrossRef]
    [Google Scholar]
  15. Georg-Fries, B., Biederlack, S., Wolf, J. & zur Hausen, H. ( 1984; ). Analysis of proteins, helper dependence, and seroepidemiology of a new human parvovirus. Virology 134, 64–71.[CrossRef]
    [Google Scholar]
  16. Greber, U. F. ( 2002; ). Signalling in viral entry. Cell Mol Life Sci 59, 608–626.[CrossRef]
    [Google Scholar]
  17. Grieger, J. C., Choi, V. W. & Samulski, R. J. ( 2006; ). Production and characterization of adeno-associated viral vectors. Nat Protoc 1, 1412–1428.[CrossRef]
    [Google Scholar]
  18. Grimm, D. & Kay, M. A. ( 2003; ). From virus evolution to vector revolution: use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors for human gene therapy. Curr Gene Ther 3, 281–304.[CrossRef]
    [Google Scholar]
  19. Harbison, C. E., Chiorini, J. A. & Parrish, C. R. ( 2008; ). The parvovirus capsid odyssey: from the cell surface to the nucleus. Trends Microbiol 16, 208–214.[CrossRef]
    [Google Scholar]
  20. Hendrie, P. C. & Russell, D. W. ( 2005; ). Gene targeting with viral vectors. Mol Ther 12, 9–17.[CrossRef]
    [Google Scholar]
  21. Kaludov, N., Brown, K. E., Walters, R. W., Zabner, J. & Chiorini, J. A. ( 2001; ). Adeno-associated virus sereotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75, 6884–6893.[CrossRef]
    [Google Scholar]
  22. Le, P. U. & Nabi, I. R. ( 2003; ). Distinct caveolae-mediated endocytic pathways target the Golgi apparatus and the endoplasmic reticulum. J Cell Sci 116, 1059–1071.[CrossRef]
    [Google Scholar]
  23. Lehmann, M. J., Sherer, N. M., Marks, C. B., Pypaert, M. & Mothes, W. ( 2005; ). Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells. J Cell Biol 170, 317–325.[CrossRef]
    [Google Scholar]
  24. Marsh, M. & Helenius, A. ( 2006; ). Virus entry: open sesame. Cell 124, 729–740.[CrossRef]
    [Google Scholar]
  25. Muzyczka, N. & Warrington, K. H., Jr ( 2005; ). Custom adeno-associated virus capsids: the next generation of recombinant vectors with novel tropism. Hum Gene Ther 16, 408–416.[CrossRef]
    [Google Scholar]
  26. Nabi, I. R. & Le, P. U. ( 2003; ). Caveolar/raft-dependent endocytosis. J Cell Biol 161, 673–677.[CrossRef]
    [Google Scholar]
  27. Nichols, B. J. ( 2002; ). A distinct class of endosomes mediates clathrin-independent endocytosis to the Golgi complex. Nat Cell Biol 4, 374–378.
    [Google Scholar]
  28. Nichols, B. J. ( 2003; ). Caveosomes and endocytosis of lipid rafts. J Cell Sci 116, 4707–4714.[CrossRef]
    [Google Scholar]
  29. Parker, J. S. & Parrish, C. R. ( 2000; ). Cellular uptake and infection by canine parvovirus involves rapid dynamin-regulated clathrin-mediated endocytosis, followed by slower intracellular trafficking. J Virol 74, 1919–1930.[CrossRef]
    [Google Scholar]
  30. Parton, R. G. & Richards, A. A. ( 2003; ). Lipid rafts and caveolae as portals for endocytosis: new insights and common mechanisms. Traffic 4, 724–738.[CrossRef]
    [Google Scholar]
  31. Pelkmans, L., Kartenbeck, J. & Helenius, A. ( 2001; ). Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 3, 473–483.[CrossRef]
    [Google Scholar]
  32. Pelkmans, L., Bürli, T., Zerial, M. & Helenius, A. ( 2004; ). Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118, 767–780.[CrossRef]
    [Google Scholar]
  33. Pietiäinen, V. M., Marjomäki, V., Heino, J. & Hyypiä, T. ( 2005; ). Viral entry, lipid rafts and caveosomes. Ann Med 37, 394–403.[CrossRef]
    [Google Scholar]
  34. Rothberg, K. G., Heuser, J. E., Donzell, W. C., Ying, Y. S., Glenney, J. R. & Anderson, R. G. ( 1992; ). Caveolin, a protein component of caveolae membrane coats. Cell 68, 673–682.[CrossRef]
    [Google Scholar]
  35. Rust, M. J., Lakadamyali, M., Zhang, F. & Zhuang, X. ( 2004; ). Assembly of endocytic machinery around individual influenza viruses during viral entry. Nat Struct Mol Biol 11, 567–573.[CrossRef]
    [Google Scholar]
  36. Srivastava, A. ( 2005; ). Hematopoietic stem cell transduction by recombinant adeno-associated virus vectors: problems and solutions. Hum Gene Ther 16, 792–798.[CrossRef]
    [Google Scholar]
  37. Vihinen-Ranta, M., Suikkanen, S. & Parrish, C. R. ( 2004; ). Pathways of cell infection by parvoviruses and adeno-associated viruses. J Virol 78, 6709–6714.[CrossRef]
    [Google Scholar]
  38. Walters, R. W., Min, S., Yi, P., Keshavjee, S., Brown, K. E., Welsh, M. J., Chiorini, J. A. & Zabner, J. ( 2001; ). Binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer. J Biol Chem 276, 20610–20616.[CrossRef]
    [Google Scholar]
  39. Warrington, K. H., Jr & Herzog, R. W. ( 2006; ). Treatment of human disease by adeno-associated viral gene transfer. Hum Genet 119, 571–603.[CrossRef]
    [Google Scholar]
  40. Wistuba, A., Weger, S., Kern, A. & Kleinschmidt, J. A. ( 1995; ). Intermediates of adeno-associated virus type 2 assembly: identification of soluble complexes containing Rep and Cap proteins. J Virol 69, 5311–5319.
    [Google Scholar]
  41. Wood, W. & Martin, P. ( 2002; ). Structures in focus – filopodia. Int J Biochem Cell Biol 34, 726–730.[CrossRef]
    [Google Scholar]
  42. Wu, Z., Asokan, A. & Samulski, R. J. ( 2006; ). Adeno-associated virus serotypes: vector toolkit for human gene therapy. Mol Ther 14, 316–327.[CrossRef]
    [Google Scholar]
  43. Xiao, W., Warrington, K. H., Jr, Hearing, P., Hughes, J. & Muzyczka, N. ( 2002; ). Adenovirus-facilitated nuclear translocation of adeno-associated virus type 2. J Virol 76, 11505–11517.[CrossRef]
    [Google Scholar]
  44. Young, J. A. T. ( 2001; ). Virus entry and uncoating. In Fields Virology, 4th edn, pp. 87–103. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  45. Zhong, L., Zhao, W., Wu, J., Maina, N., Han, Z. & Srivastava, A. ( 2006; ). Adeno-associated virus-mediated gene transfer in hematopoietic stem/progenitor cells as a therapeutic tool. Curr Gene Ther 6, 683–698.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.005595-0
Loading
/content/journal/jgv/10.1099/vir.0.005595-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error