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J Virol, June 1998, p. 5224-5230, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Recombinant Human Parvovirus B19 Vectors: Erythroid Cell-Specific Delivery and Expression of Transduced Genes

Selvarangan Ponnazhagan,1,2,3 Kirsten A. Weigel,1,2,3 Sudhanshu P. Raikwar,1,2,3 Pinku Mukherjee,2,3 Mervin C. Yoder,4 and Arun Srivastava1,2,3,5,*

Department of Microbiology & Immunology,1 Walther Oncology Center,2 Herman B. Wells Center for Pediatric Research and Department of Biochemistry & Molecular Biology,4 and Division of Hematology/Oncology, Department of Medicine,5 Indiana University School of Medicine, and Walther Cancer Institute,3 Indianapolis, Indiana 46202

Received 8 October 1997/Accepted 16 March 1998

A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562-566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111-1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited and acquired human diseases affecting cells of erythroid lineage.

* Corresponding author. Mailing address: Department of Microbiology & Immunology, Indiana University School of Medicine, 635 Barnhill Dr., Medical Science Building Room 255, Indianapolis, IN 46202-5120. Phone: (317) 274-2194. Fax: (317) 274-4090. E-mail: asrivast{at}.iupui.edu.

J Virol, June 1998, p. 5224-5230, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Weigel-Kelley, K. A., Yoder, M. C., Srivastava, A. (2003). {alpha}5{beta}1 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of {beta}1 integrin for viral entry. Blood 102: 3927-3933 [Abstract] [Full Text]  
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  • Weigel-Kelley, K. A., Yoder, M. C., Srivastava, A. (2001). Recombinant Human Parvovirus B19 Vectors: Erythrocyte P Antigen Is Necessary but Not Sufficient for Successful Transduction of Human Hematopoietic Cells. J. Virol. 75: 4110-4116 [Abstract] [Full Text]  


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