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Journal of Virology, April 1999, p. 2832-2840, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Lentivirus Vectors Using Human and Simian Immunodeficiency Virus Elements

Sarah M. White,1 Matthew Renda,1,2 Na-Yon Nam,1 Ekaterina Klimatcheva,1 Yonghong Zhu,1,2 Jennifer Fisk,1 Mark Halterman,3 Bobbie J. Rimel,1 Howard Federoff,3 Snehal Pandya,1 Joseph D. Rosenblatt,1,2 and Vicente Planelles1,2,*

Departments of Medicine,1 Microbiology and Immunology,2 and Neurology,3 University of Rochester Cancer Center, Rochester, New York 14642

Received 28 August 1998/Accepted 23 December 1998

Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34+ cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.

* Corresponding author. Mailing address: Departments of Medicine and Microbiology and Immunology, University of Rochester Cancer Center, 601 Elmwood Ave., Box 704, Rochester, NY 14642. Phone: (716) 273-4474. Fax: (716) 273-1042. E-mail: vicente_planelles{at}urmc.rochester.edu.

Journal of Virology, April 1999, p. 2832-2840, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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