Home LiteratureArticle Details
PMID: 9811719 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Adeno-associated virus type 2-mediated gene transfer: role of epidermal growth factor receptor protein tyrosine kinase in transgene expression.

Journal of virology ·Vol. 72 ·No. 12 ·1998-12-00 ·Pages 9835-43

Mah C, Qing K, Khuntirat B, Ponnazhagan S, Wang XS, Kube DM, Yoder MC, Srivastava A

Abstract

Adeno-associated virus type 2 (AAV), a single-stranded, DNA-containing, nonpathogenic human parvovirus, has gained attention as a potentially useful vector for human gene therapy. However, the transduction efficiency of AAV vectors varies greatly in different cells and tissues in vitro and in vivo. We have recently documented that a cellular tyrosine phosphoprotein, designated the single-stranded D-sequence-binding protein (ssD-BP), plays an important role in AAV-mediated transgene expression (K. Y. Qing et al., Proc. Natl. Acad. Sci. USA 94:10879-10884, 1997) and that a strong correlation exists between the phosphorylation state of the ssD-BP and AAV transduction efficiency in vitro as well as in vivo (K. Y. Qing et al., J. Virol. 72:1593-1599, 1998). In this report, we document that treatment of cells with specific inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK) activity, such as tyrphostin, leads to significant augmentation of AAV transduction efficiency, and phosphorylation of the ssD-BP is mediated by the EGF-R PTK. Treatment of cells with EGF results in phosphorylation of the ssD-BP, whereas treatment with tyrphostin causes dephosphorylation of the ssD-BP and consequently leads to increased expression of the transgene. Furthermore, AAV transduction efficiency inversely correlates with expression of the EGF-R in different cell types, and stable transfection of the EGF-R cDNA causes phosphorylation of the ssD-BP, leading to significant inhibition in AAV-mediated transgene expression which can be overcome by the tyrphostin treatment. These data suggest that the PTK activity of the EGF-R is a crucial determinant in the life cycle of AAV and that further studies on the interaction between the EGF-R and the ssD-BP may yield new insights not only into its role in the host cell but also in the successful use of AAV vectors in human gene therapy.

MeSH Terms
Cell Line DNA, Complementary/genetics DNA-Binding Proteins/metabolism Dependovirus/genetics Enzyme Inhibitors/pharmacology ErbB Receptors/genetics,metabolism Gene Expression Gene Transfer Techniques Genetic Therapy Genistein/pharmacology Humans Hydroxyurea/pharmacology Phosphorylation Transduction, Genetic/drug effects Tyrphostins/pharmacology
Chemicals
DNA, Complementary DNA-Binding Proteins Enzyme Inhibitors Tyrphostins Genistein ErbB Receptors Hydroxyurea
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Mah C
Department of Microbiology and Immunology, Indianapolis, Indiana 46202, USA.
Qing K
Khuntirat B
Ponnazhagan S
Wang X S
Kube D M
Yoder M C
Srivastava A
References (61)
61 references, click to expand
  1. Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase.
    J Biol Chem. 1994 Feb 4;269(5):3563-7 PMID: 8106399
  2. Reversion of v-H-ras-transformed NIH 3T3 cells by apigenin through inhibiting mitogen activated protein kinase and its downstream oncogenes.
    Biochem Biophys Res Commun. 1995 Jul 26;212(3):767-75 PMID: 7626110
  3. Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors.
    Science. 1994 May 27;264(5163):1319-22 PMID: 8191285
  4. Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines.
    FEBS Lett. 1994 May 23;345(1):43-6 PMID: 8194597
  5. Adeno-associated virus vectors preferentially transduce cells in S phase.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8915-9 PMID: 8090744
  6. Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation.
    Cancer Res. 1994 Dec 1;54(23):6106-14 PMID: 7954456
  7. Quick methylene blue staining for visualizing virus plaques in titration experiments.
    Biotechniques. 1994 Sep;17(3):464-5 PMID: 7529512
  8. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain.
    Nat Genet. 1994 Oct;8(2):148-54 PMID: 7842013
  9. Biochemical targets of the isoflavone genistein in tumor cell lines.
    Proc Soc Exp Biol Med. 1995 Jan;208(1):103-8 PMID: 7892283
  10. Genistein as an inducer of tumor cell differentiation: possible mechanisms of action.
    Proc Soc Exp Biol Med. 1995 Jan;208(1):109-15 PMID: 7892284
  11. Emergence of MCF-7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: evidence for a role of EGFR in breast cancer growth and progression.
    Cell Growth Differ. 1994 Dec;5(12):1263-74 PMID: 7696175
  12. DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5719-23 PMID: 7777575
  13. Rescue and replication signals of the adeno-associated virus 2 genome.
    J Mol Biol. 1995 Jul 28;250(5):573-80 PMID: 7623375
  14. The epidermal growth factor.
    Cell Biol Int. 1995 May;19(5):413-30 PMID: 7640657
  15. Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis.
    J Virol. 1996 Jan;70(1):520-32 PMID: 8523565
  16. Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors.
    J Virol. 1996 May;70(5):3227-34 PMID: 8627803
  17. Rescue and replication of adeno-associated virus type 2 as well as vector DNA sequences from recombinant plasmids containing deletions in the viral inverted terminal repeats: selective encapsidation of viral genomes in progeny virions.
    J Virol. 1996 Mar;70(3):1668-77 PMID: 8627687
  18. Effect of the protein tyrosine kinase inhibitor genistein on normal and leukaemic haemopoietic progenitor cells.
    Br J Haematol. 1996 Jun;93(3):551-7 PMID: 8652372
  19. Differential expression in human cells from the p6 promoter of human parvovirus B19 following plasmid transfection and recombinant adeno-associated virus 2 (AAV) infection: human megakaryocytic leukaemia cells are non-permissive for AAV infection.
    J Gen Virol. 1996 Jun;77 ( Pt 6):1111-22 PMID: 8683195
  20. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector.
    Brain Res. 1996 Mar 25;713(1-2):99-107 PMID: 8724980
  21. Biology of adeno-associated virus.
    Curr Top Microbiol Immunol. 1996;218:1-23 PMID: 8794242
  22. Effects of gamma irradiation on the transduction of dividing and nondividing cells in brain and muscle of rats by adeno-associated virus vectors.
    Hum Gene Ther. 1996 May 1;7(7):841-50 PMID: 8860836
  23. Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector.
    J Virol. 1996 Nov;70(11):8098-108 PMID: 8892935
  24. Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14082-7 PMID: 8943064
  25. Lack of site-specific integration of the recombinant adeno-associated virus 2 genomes in human cells.
    Hum Gene Ther. 1997 Feb 10;8(3):275-84 PMID: 9048194
  26. Recombinant adeno-associated virus for muscle directed gene therapy.
    Nat Med. 1997 Mar;3(3):306-12 PMID: 9055858
  27. Adeno-associated virus type 2 DNA replication in vivo: mutation analyses of the D sequence in viral inverted terminal repeats.
    J Virol. 1997 Apr;71(4):3077-82 PMID: 9060669
  28. Adeno-associated virus type 2-mediated transduction of murine hematopoietic cells with long-term repopulating ability and sustained expression of a human globin gene in vivo.
    J Virol. 1997 Apr;71(4):3098-104 PMID: 9060672
  29. Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice.
    Gene. 1997 Apr 29;190(1):203-10 PMID: 9185868
  30. Adeno-associated virus type 2-mediated transfer of ecotropic retrovirus receptor cDNA allows ecotropic retroviral transduction of established and primary human cells.
    J Virol. 1997 Jul;71(7):5663-7 PMID: 9188645
  31. Quantitative DNA slot blot analysis: inhibition of DNA binding to membranes by magnesium ions.
    Nucleic Acids Res. 1997 Aug 15;25(16):3375-6 PMID: 9241256
  32. Encapsidation of adeno-associated virus type 2 Rep proteins in wild-type and recombinant progeny virions: Rep-mediated growth inhibition of primary human cells.
    J Virol. 1997 Oct;71(10):7361-71 PMID: 9311814
  33. Adeno-associated virus type 2-mediated transduction in primary human bone marrow-derived CD34+ hematopoietic progenitor cells: donor variation and correlation of transgene expression with cellular differentiation.
    J Virol. 1997 Nov;71(11):8262-7 PMID: 9343178
  34. Role of tyrosine phosphorylation of a cellular protein in adeno-associated virus 2-mediated transgene expression.
    Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10879-84 PMID: 9380728
  35. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions.
    J Virol. 1998 Feb;72(2):1438-45 PMID: 9445046
  36. Adeno-associated virus type 2-mediated gene transfer: correlation of tyrosine phosphorylation of the cellular single-stranded D sequence-binding protein with transgene expression in human cells in vitro and murine tissues in vivo.
    J Virol. 1998 Feb;72(2):1593-9 PMID: 9445062
  37. Characterization of wild-type adeno-associated virus type 2-like particles generated during recombinant viral vector production and strategies for their elimination.
    J Virol. 1998 Jul;72(7):5472-80 PMID: 9621003
  38. Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2.
    Nat Med. 1999 Jan;5(1):71-7 PMID: 9883842
  39. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors.
    J Natl Cancer Inst. 1973 Nov;51(5):1417-23 PMID: 4357758
  40. Nerve growth factor receptors on human melanoma cells in culture.
    Proc Natl Acad Sci U S A. 1977 Feb;74(2):565-9 PMID: 265522
  41. Nucleotide sequence and organization of the adeno-associated virus 2 genome.
    J Virol. 1983 Feb;45(2):555-64 PMID: 6300419
  42. A rapid decrease in epidermal growth factor-binding capacity accompanies the terminal differentiation of mouse myoblasts in vitro.
    J Cell Biol. 1984 Feb;98(2):739-47 PMID: 6319433
  43. Immunoaffinity purification of the epidermal growth factor receptor. Stoichiometry of binding and kinetics of self-phosphorylation.
    J Biol Chem. 1984 Dec 10;259(23):14631-6 PMID: 6094567
  44. Reconstitution of human epidermal growth factor receptors and its deletion mutants in cultured hamster cells.
    J Biol Chem. 1986 Sep 25;261(27):12490-7 PMID: 3017977
  45. Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site.
    J Virol. 1987 Mar;61(3):858-65 PMID: 3027412
  46. Molecular evidence for the lack of epidermal growth factor receptor gene expression in small cell lung carcinoma cells.
    Cancer Res. 1987 May 15;47(10):2668-73 PMID: 3032412
  47. Genistein, a specific inhibitor of tyrosine-specific protein kinases.
    J Biol Chem. 1987 Apr 25;262(12):5592-5 PMID: 3106339
  48. Adeno-associated viruses: an update.
    Adv Virus Res. 1987;32:243-306 PMID: 3039813
  49. Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors.
    Science. 1988 Nov 11;242(4880):933-5 PMID: 3263702
  50. Tyrphostins inhibit epidermal growth factor (EGF)-receptor tyrosine kinase activity in living cells and EGF-stimulated cell proliferation.
    J Biol Chem. 1989 Aug 25;264(24):14503-9 PMID: 2788167
  51. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression.
    J Virol. 1989 Sep;63(9):3822-8 PMID: 2547998
  52. Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors.
    J Med Chem. 1989 Oct;32(10):2344-52 PMID: 2552117
  53. Tyrphostins--potential antiproliferative agents and novel molecular tools.
    Biochem Pharmacol. 1990 Sep 1;40(5):913-8 PMID: 2143901
  54. Rapid uptake of tyrphostin into A431 human epidermoid cells is followed by delayed inhibition of epidermal growth factor (EGF)-stimulated EGF receptor tyrosine kinase activity.
    Mol Cell Biol. 1991 May;11(5):2697-703 PMID: 1850101
  55. Specific inhibition of cytoplasmic protein tyrosine kinases by herbimycin A in vitro.
    Biochem Pharmacol. 1991 Oct 9;42(9):1661-71 PMID: 1656993
  56. Inhibition of protein-tyrosine kinases by tyrphostins.
    Methods Enzymol. 1991;201:347-61 PMID: 1658552
  57. Use of adeno-associated virus as a general transduction vector for mammalian cells.
    Curr Top Microbiol Immunol. 1992;158:97-129 PMID: 1316261
  58. Large-scale purification and characterisation of a recombinant epidermal growth-factor receptor protein-tyrosine kinase. Modulation of activity by multiple factors.
    Eur J Biochem. 1992 Jul 1;207(1):265-75 PMID: 1321046
  59. Versatile adeno-associated virus 2-based vectors for constructing recombinant virions.
    Gene. 1993 Feb 28;124(2):257-62 PMID: 8383071
  60. Epidermal growth factor receptor expression in demented elderly: localization to vascular endothelial cells of brain, pituitary and skin.
    Brain Res. 1993 Jul 2;615(2):181-90 PMID: 7689911
  61. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
    J Biol Chem. 1994 Feb 18;269(7):5241-8 PMID: 8106507
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.12.9835-9843.1998
Published
1998-12-00
Pages
9835-43
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110495
Subset
IM
Grants
NHLBI NIH HHS · HL-58881 · United States
NHLBI NIH HHS · P01 HL053586 · United States
NHLBI NIH HHS · HL-48342 · United States
NHLBI NIH HHS · HL-53586 · United States
NIDDK NIH HHS · P50 DK049218 · United States
NHLBI NIH HHS · R01 HL058881 · United States
NIDDK NIH HHS · P30 DK049218 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.12.9835-9843.1998 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2