This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lusky, M.
Right arrow Articles by Mehtali, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lusky, M.
Right arrow Articles by Mehtali, M.

 Previous Article  |  Next Article 

J Virol, March 1998, p. 2022-2032, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro and In Vivo Biology of Recombinant Adenovirus Vectors with E1, E1/E2A, or E1/E4 Deleted

M. Lusky, M. Christ, K. Rittner, A. Dieterle, D. Dreyer, B. Mourot, H. Schultz, F. Stoeckel, A. Pavirani, and M. Mehtali*

Transgène S.A., 67000 Strasbourg, France

Received 21 August 1997/Accepted 17 November 1997

Isogenic, E3-deleted adenovirus vectors defective in E1, E1 and E2A, or E1 and E4 were generated in complementation cell lines expressing E1, E1 and E2A, or E1 and E4 and characterized in vitro and in vivo. In the absence of complementation, deletion of both E1 and E2A completely abolished expression of early and late viral genes, while deletion of E1 and E4 impaired expression of viral genes, although at a lower level than the E1/E2A deletion. The in vivo persistence of these three types of vectors was monitored in selected strains of mice with viral genomes devoid of transgenes to exclude any interference by immunogenic transgene-encoded products. Our studies showed no significant differences among the vectors in the short-term maintenance and long-term (4-month) persistence of viral DNA in liver and lung cells of immunocompetent and immunodeficient mice. Furthermore, all vectors induced similar antibody responses and comparable levels of adenovirus-specific cytotoxic T lymphocytes. These results suggest that in the absence of transgenes, the progressive deletion of the adenovirus genome does not extend the in vivo persistence of the transduced cells and does not reduce the antivirus immune response. In addition, our data confirm that, in the absence of transgene expression, mouse cellular immunity to viral antigens plays a minor role in the progressive elimination of the virus genome.

* Corresponding author. Mailing address: Transgène S.A., 11 rue de Molsheim, 67000 Strasbourg, France. Phone: 33 388 27 91 00. Fax: 33 388 27 91 11. E-mail: mehtali{at}transgene.fr.




This article has been cited by other articles:

  • Scheller, E.L., Krebsbach, P.H. (2009). Gene Therapy: Design and Prospects for Craniofacial Regeneration. JDR 88: 585-596 [Abstract] [Full Text]  
  • Narang, A. S., Mahato, R. I. (2006). Biological and biomaterial approaches for improved islet transplantation.. Pharmacol. Rev. 58: 194-243 [Abstract] [Full Text]  
  • Catalucci, D., Sporeno, E., Cirillo, A., Ciliberto, G., Nicosia, A., Colloca, S. (2005). An Adenovirus Type 5 (Ad5) Amplicon-Based Packaging Cell Line for Production of High-Capacity Helper-Independent {Delta}E1-E2-E3-E4 Ad5 Vectors. J. Virol. 79: 6400-6409 [Abstract] [Full Text]  
  • Wen, S., Graf, S., Massey, P. G., Dichek, D. A. (2004). Improved Vascular Gene Transfer With a Helper-Dependent Adenoviral Vector. Circulation 110: 1484-1491 [Abstract] [Full Text]  
  • Stilwell, J. L., McCarty, D. M., Negishi, A., Superfine, R., Samulski, R. J. (2003). Development and Characterization of Novel Empty Adenovirus Capsids and Their Impact on Cellular Gene Expression. J. Virol. 77: 12881-12885 [Abstract] [Full Text]  
  • Ehrhardt, A., Xu, H., Dillow, A. M., Bellinger, D. A., Nichols, T. C., Kay, M. A. (2003). A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102: 2403-2411 [Abstract] [Full Text]  
  • Molinier-Frenkel, V., Prevost-Blondel, A., Hong, S.-S., Lengagne, R., Boudaly, S., Magnusson, M. K., Boulanger, P., Guillet, J.-G. (2003). The Maturation of Murine Dendritic Cells Induced by Human Adenovirus Is Mediated by the Fiber Knob Domain. J. Biol. Chem. 278: 37175-37182 [Abstract] [Full Text]  
  • Davies, E. L., Ramsden, J. D., Cocks, H., Searle, P. F., Watkinson, J. C., Ueno, H., Logan, A., Franklyn, J. A., Mautner, V., Eggo, M. C. (2003). Adenovirus-Mediated Expression of Dominant Negative Fibroblast Growth Factor (FGF) Receptor 1 in Thyroid Cells Blocks FGF Effects and Reduces Goitrogenesis in Mice. J. Clin. Endocrinol. Metab. 88: 4472-4480 [Abstract] [Full Text]  
  • Ehrhardt, A., Xu, H., Kay, M. A. (2003). Episomal Persistence of Recombinant Adenoviral Vector Genomes during the Cell Cycle In Vivo. J. Virol. 77: 7689-7695 [Abstract] [Full Text]  
  • Imbert, I., Dimitrova, M., Kien, F., Kieny, M. P., Schuster, C. (2003). Hepatitis C virus IRES efficiency is unaffected by the genomic RNA 3'NTR even in the presence of viral structural or non-structural proteins. J. Gen. Virol. 84: 1549-1557 [Abstract] [Full Text]  
  • Dimitrova, M., Imbert, I., Kieny, M. P., Schuster, C. (2003). Protein-Protein Interactions between Hepatitis C Virus Nonstructural Proteins. J. Virol. 77: 5401-5414 [Abstract] [Full Text]  
  • Himoudi, N., Abraham, J.-D., Fournillier, A., Lone, Y. C., Joubert, A., De Beeck, A. O., Freida, D., Lemonnier, F., Kieny, M. P., Inchauspe, G. (2002). Comparative Vaccine Studies in HLA-A2.1-Transgenic Mice Reveal a Clustered Organization of Epitopes Presented in Hepatitis C Virus Natural Infection. J. Virol. 76: 12735-12746 [Abstract] [Full Text]  
  • Gordon, J. W. (2002). Adenovirus gene transfer vector toxicity to mouse embryos: implications for human IVF. Hum Reprod 17: 2380-2387 [Abstract] [Full Text]  
  • Molinier-Frenkel, V., Lengagne, R., Gaden, F., Hong, S.-S., Choppin, J., Gahery-Segard, H., Boulanger, P., Guillet, J.-G. (2002). Adenovirus Hexon Protein Is a Potent Adjuvant for Activation of a Cellular Immune Response. J. Virol. 76: 127-135 [Abstract] [Full Text]  
  • Zhang, W., Low, J. A., Christensen, J. B., Imperiale, M. J. (2001). Role for the Adenovirus IVa2 Protein in Packaging of Viral DNA. J. Virol. 75: 10446-10454 [Abstract] [Full Text]  
  • YOUNG, L S, MAUTNER, V (2001). The promise and potential hazards of adenovirus gene therapy. Gut 48: 733-736 [Full Text]  
  • Chanson, M., Berclaz, P.-Y., Scerri, I., Dudez, T., Wernke-Dollries, K., Pizurki, L., Pavirani, A., Fiedler, M. A., Suter, S. (2001). Regulation of Gap Junctional Communication by a Pro-Inflammatory Cytokine in Cystic Fibrosis Transmembrane Conductance Regulator-Expressing but Not Cystic Fibrosis Airway Cells. Am. J. Pathol. 158: 1775-1784 [Abstract] [Full Text]  
  • Russell, W. C. (2000). Update on adenovirus and its vectors. J. Gen. Virol. 81: 2573-2604 [Full Text]  
  • Molinier-Frenkel, V., Gahery-Segard, H., Mehtali, M., Le Boulaire, C., Ribault, S., Boulanger, P., Tursz, T., Guillet, J.-G., Farace, F. (2000). Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes. J. Virol. 74: 7678-7682 [Abstract] [Full Text]  
  • Erbs, P., Regulier, E., Kintz, J., Leroy, P., Poitevin, Y., Exinger, F., Jund, R., Mehtali, M. (2000). In Vivo Cancer Gene Therapy by Adenovirus-mediated Transfer of a Bifunctional Yeast Cytosine Deaminase/Uracil Phosphoribosyltransferase Fusion Gene. Cancer Res. 60: 3813-3822 [Abstract] [Full Text]  
  • Pizurki, L., Morris, M. A., Chanson, M., Solomon, M., Pavirani, A., Bouchardy, I., Suter, S. (2000). Cystic Fibrosis Transmembrane Conductance Regulator Does Not Affect Neutrophil Migration across Cystic Fibrosis Airway Epithelial Monolayers. Am. J. Pathol. 156: 1407-1416 [Abstract] [Full Text]  
  • Sandig, V., Youil, R., Bett, A. J., Franlin, L. L., Oshima, M., Maione, D., Wang, F., Metzker, M. L., Savino, R., Caskey, C. T. (2000). Optimization of the helper-dependent adenovirus system for production and potency in vivo. Proc. Natl. Acad. Sci. USA 97: 1002-1007 [Abstract] [Full Text]  
  • Rea, D., Schagen, F. H. E., Hoeben, R. C., Mehtali, M., Havenga, M. J. E., Toes, R. E. M., Melief, C. J. M., Offringa, R. (1999). Adenoviruses Activate Human Dendritic Cells without Polarization toward a T-Helper Type 1-Inducing Subset. J. Virol. 73: 10245-10253 [Abstract] [Full Text]  
  • Parks, R. J., Bramson, J. L., Wan, Y., Addison, C. L., Graham, F. L. (1999). Effects of Stuffer DNA on Transgene Expression from Helper-Dependent Adenovirus Vectors. J. Virol. 73: 8027-8034 [Abstract] [Full Text]  
  • Lusky, M., Grave, L., Dieterle, A., Dreyer, D., Christ, M., Ziller, C., Furstenberger, P., Kintz, J., Ali Hadji, D., Pavirani, A., Mehtali, M. (1999). Regulation of Adenovirus-Mediated Transgene Expression by the Viral E4 Gene Products: Requirement for E4 ORF3. J. Virol. 73: 8308-8319 [Abstract] [Full Text]  
  • Harvey, B.-G., Hackett, N. R., El-Sawy, T., Rosengart, T. K., Hirschowitz, E. A., Lieberman, M. D., Lesser, M. L., Crystal, R. G. (1999). Variability of Human Systemic Humoral Immune Responses to Adenovirus Gene Transfer Vectors Administered to Different Organs. J. Virol. 73: 6729-6742 [Abstract] [Full Text]  
  • Gorziglia, M. I., Lapcevich, C., Roy, S., Kang, Q., Kadan, M., Wu, V., Pechan, P., Kaleko, M. (1999). Generation of an Adenovirus Vector Lacking E1, E2a, E3, and All of E4 except Open Reading Frame 3. J. Virol. 73: 6048-6055 [Abstract] [Full Text]  
  • Schowalter, D. B., Himeda, C. L., Winther, B. L., Wilson, C. B., Kay, M. A. (1999). Implication of Interfering Antibody Formation and Apoptosis as Two Different Mechanisms Leading to Variable Duration of Adenovirus-Mediated Transgene Expression in Immune-Competent Mice. J. Virol. 73: 4755-4766 [Abstract] [Full Text]  
  • Legrand, V., Spehner, D., Schlesinger, Y., Settelen, N., Pavirani, A., Mehtali, M. (1999). Fiberless Recombinant Adenoviruses: Virus Maturation and Infectivity in the Absence of Fiber. J. Virol. 73: 907-919 [Abstract] [Full Text]  
  • Moorhead, J. W., Clayton, G. H., Smith, R. L., Schaack, J. (1999). A Replication-Incompetent Adenovirus Vector with the Preterminal Protein Gene Deleted Efficiently Transduces Mouse Ears. J. Virol. 73: 1046-1053 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»