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Journal of Virology, May 2001, p. 4110-4116, Vol. 75, No. 9
Department of Microbiology and
Immunology,1 Walther Oncology
Center,2 Herman B. Wells Center for
Pediatric Research and Department of Biochemistry and Molecular
Biology,3 and Division of
Hematology/Oncology,4 Department of
Medicine, Walther Cancer Institute, Indiana University School of
Medicine, Indianapolis, Indiana 46202-5120
Received 22 November 2000/Accepted 8 February 2001
The blood group P antigen, known to be abundantly expressed on
erythroid cells, has been reported to be the cellular receptor for
parvovirus B19. We have described the development of recombinant parvovirus B19 vectors with which high-efficiency, erythroid
lineage-restricted transduction can be achieved (S. Ponnazhagan,
K. A. Weigel, S. P. Raikwar, P. Mukherjee, M. C. Yoder,
and A. Srivastava, J. Virol. 72:5224-5230, 1998).
However, since a low-level transduction of nonerythroid cells could
also be detected and since P antigen is expressed in nonerythroid
cells, we reevaluated the role of P antigen in the viral binding and
entry into cells. Cell surface expression analyses revealed that
~75% of primary human bone marrow mononuclear erythroid cells and
~31% of cells in the nonerythroid population were positive for P
antigen. Two human erythroleukemia cell lines, HEL and K562, and a
human promyelocytic leukemia cell line, HL-60, were also examined for P
antigen expression and binding and entry of the vector. HEL and K562
cells showed intermediate levels, whereas HL-60 cells demonstrated high
levels of expression of P antigen. However, the efficiency of vector
binding to these cells did not correlate with P antigen expression.
Moreover, despite P antigen positivity and efficient viral binding,
HEL, K562, and HL-60 cells could not be transduced with the vector. Low
levels of P antigen expression could also be detected in two primary cell types, human umbilical vein endothelial cells (HUVEC) and normal
human lung fibroblasts (NHLF). In addition, vector binding occurred in
both cell types and was inhibited by globoside, indicating the
involvement of P antigen in virus binding to these cells. These primary
cells could be efficiently transduced with the recombinant vector.
These data suggest that (i) P antigen is expressed on a variety of cell
types and is involved in binding of parvovirus B19 to human cells, (ii)
the level of P antigen expression does not correlate with the
efficiency of viral binding, (iii) P antigen is necessary but not
sufficient for parvovirus B19 entry into cells, and (iv) parvovirus B19
vectors can be used to transduce HUVEC and NHLF. These studies further
suggest the existence of a putative cellular coreceptor for efficient
entry of parvovirus B19 into human cells.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4110-4116.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Recombinant Human Parvovirus B19 Vectors: Erythrocyte P Antigen
Is Necessary but Not Sufficient for Successful Transduction of
Human Hematopoietic Cells
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, 635 Barnhill Dr., Medical Science
Building, Room 247, Indiana University School of Medicine,
Indianapolis, IN 46202-5120. Phone: (317) 274-2194. Fax: (317)
274-4090. E-mail: asrivast{at}iupui.edu.
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