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Blood, 1 December 2003, Vol. 102, No. 12, pp. 3927-3933. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-05-1522. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1522v1 102/12/3927    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weigel-Kelley, K. A. Articles by Srivastava, A. Search for Related Content PubMed PubMed Citation Articles by Weigel-Kelley, K. A. Articles by Srivastava, A. Related Collections Hematopoiesis and Stem Cells Red Cells Cell Adhesion and Motility Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY 51 integrin as a cellular coreceptor for human parvovirus B19: requirement of functional activation of 1 integrin for viral entry Kirsten A. Weigel-Kelley, Mervin C. Yoder, and Arun Srivastava From the Departments of Microbiology and Immunology, and Biochemistry and Molecular Biology, Indiana University School of Medicine; Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine; Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; and Walther Oncology Center, Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, IN. Replication of the pathogenic human parvovirus B19 is restricted to erythroid progenitor cells. Although blood group P antigen has been reported to be the cell surface receptor for parvovirus B19, a number of nonerythroid cells, which express P antigen, are not permissive for parvovirus B19 infection. We have documented that P antigen is necessary for parvovirus B19 binding but not sufficient for virus entry into cells. To test whether parvovirus B19 utilizes a cell surface coreceptor for entry, we used human erythroleukemia cells (K562), which allow parvovirus B19 binding but not entry. We report here that upon treatment with phorbol esters, K562 cells become adherent and permissive for parvovirus B19 entry, which is mediated by 51 integrins, but only in their high-affinity conformation. Mature human red blood cells (RBCs), which express high levels of P antigen, but not 51 integrins, bind parvovirus B19 but do not allow viral entry. In contrast, primary human erythroid progenitor cells express high levels of both P antigen and 51 integrins and allow 1 integrin–mediated entry of parvovirus B19. Thus, in a natural course of infection, RBCs are likely exploited for a highly efficient systemic dissemination of parvovirus B19. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Wong, N. Zhi, C. Filippone, K. Keyvanfar, S. Kajigaya, K. E. Brown, and N. S. Young Ex Vivo-Generated CD36+ Erythroid Progenitors Are Highly Permissive to Human Parvovirus B19 Replication J. Virol., March 1, 2008; 82(5): 2470 - 2476. [Abstract] [Full Text] [PDF] M. Waldman and J. B. Kopp Parvovirus B19 and the Kidney Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(Supplement_1): S47 - S56. [Abstract] [Full Text] [PDF] J. R. Kerr and N. Boschetti Short regions of sequence identity between the genomes of human and rodent parvoviruses and their respective hosts occur within host genes for the cytoskeleton, cell adhesion and Wnt signalling J. Gen. Virol., December 1, 2006; 87(12): 3567 - 3575. [Abstract] [Full Text] [PDF] A. Lupescu, C.-T. Bock, P. A. Lang, S. Aberle, H. Kaiser, R. Kandolf, and F. Lang Phospholipase A2 Activity-Dependent Stimulation of Ca2+ Entry by Human Parvovirus B19 Capsid Protein VP1 J. Virol., November 15, 2006; 80(22): 11370 - 11380. [Abstract] [Full Text] [PDF] A. Asokan, J. B. Hamra, L. Govindasamy, M. Agbandje-McKenna, and R. J. Samulski Adeno-Associated Virus Type 2 Contains an Integrin {alpha}5{beta}1 Binding Domain Essential for Viral Cell Entry. J. Virol., September 1, 2006; 80(18): 8961 - 8969. [Abstract] [Full Text] [PDF] M. Esfandiarei, A. Suarez, A. Amaral, X. Si, M. Rahmani, S. Dedhar, and B. M. 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