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 Sutton, R. E.
Right arrow Articles by Brown, P. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sutton, R. E.
Right arrow Articles by Brown, P. O.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 3649-3660, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Transduction of Human Progenitor Hematopoietic Stem Cells by Human Immunodeficiency Virus Type 1-Based Vectors Is Cell Cycle Dependent

Richard E. Sutton,1,* Michael J. Reitsma,2 Nobuko Uchida,2 and Patrick O. Brown3

Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 770301; SyStemix Incorporated, Palo Alto, California 943042; and Department of Biochemistry and Howard Hughes Medical Institute, Beckman Center, Stanford University Medical Center, Stanford, California 943053

Received 5 October 1998/Accepted 18 January 1999

Human immunodeficiency virus (HIV) type 1 vectors are highly efficient in their ability to transduce human progenitor hematopoietic stem cells (PHSC). Although mitosis was not required for transduction of these cells, transduction rates were much greater once cells had been cultured in the presence of cytokines. Transduction rates, however, rarely exceeded 70%. We demonstrate here that there is a distinct subpopulation that is more easily transduced by HIV vectors. These cells were distinguished by a disproportionate population in the S/G2/M phases of the cell cycle. By sorting them prior to transduction, we found that those cells in either the G1 or S/G2/M fraction were more readily transduced than G0 cells. Maintaining the cells in G0 by omitting cytokines from the medium reduced transduction rates by up to 10-fold. Addition of cytokines to the medium immediately after transduction did not improve the transduction efficiency as measured by expression of the transgene. Analysis of replication intermediates indicated that the block to transduction of G0 cells operated near the time of initiation of reverse transcription. These results suggest that although lentivirus vectors can transduce nondividing PHSC, transduction efficiency is severalfold greater once the cells exit G0 and enter G1. Further characterization of these more transducible cells and identification of the cellular factors responsible may enhance transduction while maintaining the pluripotentiality of the PHSC.

* Corresponding author. Mailing address: Division of Molecular Virology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4096. Fax: (713) 798-3586. E-mail: rsutton{at}bcm.tmc.edu.

Journal of Virology, May 1999, p. 3649-3660, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Frecha, C., Costa, C., Levy, C., Negre, D., Russell, S. J., Maisner, A., Salles, G., Peng, K.-W., Cosset, F.-L., Verhoeyen, E. (2009). Efficient and stable transduction of resting B lymphocytes and primary chronic lymphocyte leukemia cells using measles virus gp displaying lentiviral vectors. Blood 114: 3173-3180 [Abstract] [Full Text]  
  • Agosto, L. M., Yu, J. J., Liszewski, M. K., Baytop, C., Korokhov, N., Humeau, L. M., O'Doherty, U. (2009). The CXCR4-Tropic Human Immunodeficiency Virus Envelope Promotes More-Efficient Gene Delivery to Resting CD4+ T Cells than the Vesicular Stomatitis Virus Glycoprotein G Envelope. J. Virol. 83: 8153-8162 [Abstract] [Full Text]  
  • Verhoeyen, E., Cosset, F.-L. (2009). Engineering the Surface Glycoproteins of Lentiviral Vectors for Targeted Gene Transfer. CSH Protocols 2009: pdb.top59-pdb.top59 [Abstract] [Full Text]  
  • Frecha, C., Costa, C., Negre, D., Gauthier, E., Russell, S. J., Cosset, F.-L., Verhoeyen, E. (2008). Stable transduction of quiescent T cells without induction of cycle progression by a novel lentiviral vector pseudotyped with measles virus glycoproteins. Blood 112: 4843-4852 [Abstract] [Full Text]  
  • Larochelle, A., Krouse, A., Metzger, M., Orlic, D., Donahue, R. E., Fricker, S., Bridger, G., Dunbar, C. E., Hematti, P. (2006). AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood 107: 3772-3778 [Abstract] [Full Text]  
  • Lagresle-Peyrou, C., Yates, F., Malassis-Seris, M., Hue, C., Morillon, E., Garrigue, A., Liu, A., Hajdari, P., Stockholm, D., Danos, O., Lemercier, B., Gougeon, M.-L., Rieux-Laucat, F., de Villartay, J.-P., Fischer, A., Cavazzana-Calvo, M. (2006). Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity. Blood 107: 63-72 [Abstract] [Full Text]  
  • Verhoeyen, E., Wiznerowicz, M., Olivier, D., Izac, B., Trono, D., Dubart-Kupperschmitt, A., Cosset, F.-L. (2005). Novel lentiviral vectors displaying "early-acting cytokines" selectively promote survival and transduction of NOD/SCID repopulating human hematopoietic stem cells. Blood 106: 3386-3395 [Abstract] [Full Text]  
  • Liu, B., Daviau, J., Nichols, C. N., Strayer, D. S. (2005). In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors. Blood 106: 2655-2662 [Abstract] [Full Text]  
  • Consiglio, A., Gritti, A., Dolcetta, D., Follenzi, A., Bordignon, C., Gage, F. H., Vescovi, A. L., Naldini, L. (2004). From the Cover: Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors. Proc. Natl. Acad. Sci. USA 101: 14835-14840 [Abstract] [Full Text]  
  • Logan, A. C., Haas, D. L., Kafri, T., Kohn, D. B. (2004). Integrated Self-Inactivating Lentiviral Vectors Produce Full-Length Genomic Transcripts Competent for Encapsidation and Integration. J. Virol. 78: 8421-8436 [Abstract] [Full Text]  
  • Daniel, R., Greger, J. G., Katz, R. A., Taganov, K. D., Wu, X., Kappes, J. C., Skalka, A. M. (2004). Evidence that Stable Retroviral Transduction and Cell Survival following DNA Integration Depend on Components of the Nonhomologous End Joining Repair Pathway. J. Virol. 78: 8573-8581 [Abstract] [Full Text]  
  • Hanawa, H., Hematti, P., Keyvanfar, K., Metzger, M. E., Krouse, A., Donahue, R. E., Kepes, S., Gray, J., Dunbar, C. E., Persons, D. A., Nienhuis, A. W. (2004). Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus-based lentiviral vector system. Blood 103: 4062-4069 [Abstract] [Full Text]  
  • Greger, J. G., Katz, R. A., Taganov, K., Rall, G. F., Skalka, A. M. (2004). Transduction of Terminally Differentiated Neurons by Avian Sarcoma Virus. J. Virol. 78: 4902-4906 [Abstract] [Full Text]  
  • Kahn, J., Byk, T., Jansson-Sjostrand, L., Petit, I., Shivtiel, S., Nagler, A., Hardan, I., Deutsch, V., Gazit, Z., Gazit, D., Karlsson, S., Lapidot, T. (2004). Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation. Blood 103: 2942-2949 [Abstract] [Full Text]  
  • Levasseur, D. N., Ryan, T. M., Pawlik, K. M., Townes, T. M. (2003). Correction of a mouse model of sickle cell disease: lentiviral/antisickling {beta}-globin gene transduction of unmobilized, purified hematopoietic stem cells. Blood 102: 4312-4319 [Abstract] [Full Text]  
  • Fleury, S., Simeoni, E., Zuppinger, C., Deglon, N., von Segesser, L. K., Kappenberger, L., Vassalli, G. (2003). Multiply Attenuated, Self-Inactivating Lentiviral Vectors Efficiently Deliver and Express Genes for Extended Periods of Time in Adult Rat Cardiomyocytes In Vivo. Circulation 107: 2375-2382 [Abstract] [Full Text]  
  • Rivella, S., May, C., Chadburn, A., Riviere, I., Sadelain, M. (2003). A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta -globin gene transfer. Blood 101: 2932-2939 [Abstract] [Full Text]  
  • VandenDriessche, T., Thorrez, L., Naldini, L., Follenzi, A., Moons, L., Berneman, Z., Collen, D., Chuah, M. K. L. (2002). Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo. Blood 100: 813-822 [Abstract] [Full Text]  
  • Srinivasakumar, N., Zaboikin, M., Zaboikina, T., Schuening, F. (2002). Evaluation of Tat-Encoding Bicistronic Human Immunodeficiency Virus Type 1 Gene Transfer Vectors in Primary Canine Bone Marrow Mononuclear Cells. J. Virol. 76: 7334-7342 [Abstract] [Full Text]  
  • Katz, R. A., Greger, J. G., Darby, K., Boimel, P., Rall, G. F., Skalka, A. M. (2002). Transduction of Interphase Cells by Avian Sarcoma Virus. J. Virol. 76: 5422-5434 [Abstract] [Full Text]  
  • Maurice, M., Verhoeyen, E., Salmon, P., Trono, D., Russell, S. J., Cosset, F.-L. (2002). Efficient gene transfer into human primary blood lymphocytes by surface-engineered lentiviral vectors that display a T cell-activating polypeptide. Blood 99: 2342-2350 [Abstract] [Full Text]  
  • Kuhn, U., Terunuma, A., Pfutzner, W., Foster, R. A., Vogel, J. C. (2002). In Vivo Assessment of Gene Delivery to Keratinocytes by Lentiviral Vectors. J. Virol. 76: 1496-1504 [Abstract] [Full Text]  
  • Dao, M. A., Hwa, J., Nolta, J. A. (2002). Molecular mechanism of transforming growth factor beta -mediated cell-cycle modulation in primary human CD34+ progenitors. Blood 99: 499-506 [Abstract] [Full Text]  
  • Walters, M. C., Nienhuis, A. W., Vichinsky, E. (2002). Novel Therapeutic Approaches in Sickle Cell Disease. ASH Education Book 2002: 10-34 [Abstract] [Full Text]  
  • An, D. S., Kung, S. K. P., Bonifacino, A., Wersto, R. P., Metzger, M. E., Agricola, B. A., Mao, S. H., Chen, I. S. Y., Donahue, R. E. (2001). Lentivirus Vector-Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques. J. Virol. 75: 3547-3555 [Abstract] [Full Text]  
  • Mikkola, H., Woods, N.-B., Sjögren, M., Helgadottir, H., Hamaguchi, I., Jacobsen, S.-E., Trono, D., Karlsson, S. (2000). Lentivirus Gene Transfer in Murine Hematopoietic Progenitor Cells Is Compromised by a Delay in Proviral Integration and Results in Transduction Mosaicism and Heterogeneous Gene Expression in Progeny Cells. J. Virol. 74: 11911-11918 [Abstract] [Full Text]  
  • Sirven, A., Pflumio, F., Zennou, V., Titeux, M., Vainchenker, W., Coulombel, L., Dubart-Kupperschmitt, A., Charneau, P. (2000). The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood 96: 4103-4110 [Abstract] [Full Text]  
  • Woods, N.-B., Fahlman, C., Mikkola, H., Hamaguchi, I., Olsson, K., Zufferey, R., Jacobsen, S. E., Trono, D., Karlsson, S. (2000). Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells. Blood 96: 3725-3733 [Abstract] [Full Text]  
  • Barrette, S., Douglas, J. L., Seidel, N. E., Bodine, D. M. (2000). Lentivirus-based vectors transduce mouse hematopoietic stem cells with similar efficiency to Moloney murine leukemia virus-based vectors. Blood 96: 3385-3391 [Abstract] [Full Text]  
  • Salmon, P., Kindler, V., Ducrey, O., Chapuis, B., Zubler, R. H., Trono, D. (2000). High-level transgene expression in human hematopoietic progenitors and differentiated blood lineages after transduction with improved lentiviral vectors. Blood 96: 3392-3398 [Abstract] [Full Text]  
  • Park, F., Ohashi, K., Kay, M. A. (2000). Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. Blood 96: 1173-1176 [Abstract] [Full Text]  
  • Lieber, A., Kay, M. A., Li, Z.-Y. (2000). Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells. J. Virol. 74: 721-734 [Abstract] [Full Text]  
  • Williams, D. A., Nienhuis, A. W., Hawley, R. G., Smith, F. O. (2000). Gene Therapy 2000. ASH Education Book 2000: 376-393 [Abstract] [Full Text]  
  • Zhang, Z., Schuler, T., Zupancic, M., Wietgrefe, S., Staskus, K. A., Reimann, K. A., Reinhart, T. A., Rogan, M., Cavert, W., Miller, C. J., Veazey, R. S., Notermans, D., Little, S., Danner, S. A., Richman, D. D., Havlir, D., Wong, J., Jordan, H. L., Schacker, T. W., Racz, P., Tenner-Racz, K., Letvin, N. L., Wolinsky, S., Haase, A. T. (1999). Sexual Transmission and Propagation of SIV and HIV in Resting and Activated CD4+ T Cells. Science 286: 1353-1357 [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»