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Journal of Virology, February 2000, p. 1457-1467, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Adenovirus Types 11p and 35p Show High Binding Efficiencies for Committed Hematopoietic Cell Lines and Are Infective to These Cell Lines

Anna Segerman,* Ya-Fang Mei, and Göran Wadell

Department of Virology, Umeå University, 901 85 Umeå, Sweden

Received 14 July 1999/Accepted 27 October 1999

Hematopoietic cells are attractive targets for gene therapy. However, no satisfactory vectors are currently available. A major problem with the most commonly used adenovirus vectors, based on adenovirus type 2 (Ad2) or Ad5, is their low binding efficiency for hematopoietic cells. In this study we identify two adenovirus serotypes with high affinity for hematopoietic cells. The binding efficiency of prototype serotypes Ad4p, Ad11p, and Ad35p for different committed hematopoietic cell lines representing T cells (Jurkat), B cells (DG75), monocytes (U937-2), myeloblasts (K562), and granulocytes (HL-60) was evaluated and compared to that of Ad5v, the commonly used adenovirus vector, using flow cytometry. In contrast to Ad5v, which bound to less than 10% of the cells in all experiments, Ad11p and Ad35p showed high binding efficiency for all of the different hematopoietic cell lines. Ad4p bound to the lymphocytic cell lines to some extent but less well to the myelomonocytic cell lines. The abilities of the different serotypes to infect, replicate, and form complete infectious particles in the hematopoietic cell lines were also investigated by immunostaining, 35S labeling of viral proteins, and titrations of cell lysates. Ad11p and Ad35p infected the highest proportion of cells, and Ad11p infected all of the cell lines investigated. The Ad11p hexon was expressed equally well in K562 and A549 cells. Jurkat cells also showed high levels of expression of Ad11p hexons, but the production of infectious particles was low. The binding properties of virions were correlated to their ability to infect and be expressed.

* Corresponding author. Mailing address: Department of Virology, Umeå University, 901 85 Umeå, Sweden. Phone: 46907852879. Fax: 4690129905. E-mail: Anna.Segerman{at}climi.umu.se.

Journal of Virology, February 2000, p. 1457-1467, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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