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Journal of Virology, February 2000, p. 1286-1295, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Marking and Gene Expression by a Lentivirus Vector in Transplanted Human and Nonhuman Primate CD34+ Cells

Dong Sung An,1 Robert P. Wersto,2 Brian A. Agricola,2 Mark E. Metzger,2 Stephanie Lu,1 Rafael G. Amado,3 Irvin S. Y. Chen,1,* and Robert E. Donahue2

Hematology Branch, National Heart, Lung, and Blood Institute, Rockville, Maryland,2 and UCLA AIDS Institute1 and Department of Microbiology and Immunology and Molecular Genetics and Department of Medicine,3 University of California, Los Angeles, Los Angeles, California

Received 28 July 1999/Accepted 27 October 1999

Recently, gene delivery vectors based on human immunodeficiency virus (HIV) have been developed as an alternative mode of gene delivery. These vectors have a number of advantages, particularly in regard to the ability to infect cells which are not actively dividing. However, the use of vectors based on human immunodeficiency virus raises a number of issues, not the least of which is safety; therefore, further characterization of marking and gene expression in different hematopoietic lineages in primate animal model systems is desirable. We use two animal model systems for gene therapy to test the efficiency of transduction and marking, as well as the safety of these vectors. The first utilizes the rhesus animal model for cytokine-mobilized autologous peripheral blood CD34+ cell transplantation. The second uses the SCID-human (SCID-hu) thymus/liver chimeric graft animal model useful specifically for human T-lymphoid progenitor cell reconstitution. In the rhesus macaques, detectable levels of vector were observed in granulocytes, lymphocytes, monocytes, and, in one animal with the highest levels of marking, erythrocytes and platelets. In transplanted SCID-hu mice, we directly compared marking and gene expression of the lentivirus vector and a murine leukemia virus-derived vector in thymocytes. Marking was observed at comparable levels, but the lentivirus vector bearing an internal cytomegalovirus promoter expressed less efficiently than did the murine retroviral vector expressed from its own long terminal repeats. In assays for infectious HIV type 1 (HIV-1), no replication-competent HIV-1 was detected in either animal model system. Thus, these results indicate that while lentivirus vectors have no apparent deleterious effects and may have advantages over murine retroviral vectors, further study of the requirements for optimal use are warranted.

* Corresponding author. Mailing address: 10833 LeConte Ave., 11-934 Factor Building, Los Angeles, CA 90095-1678. Phone: (310) 825-4793. Fax: (310) 794-7682. E-mail: rtaweesu{at}ucla.edu.

Journal of Virology, February 2000, p. 1286-1295, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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