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Journal of Virology, August 2001, p. 7717-7722, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7717-7722.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Effective Human Herpesvirus 8 Infection of Human Umbilical Vein Endothelial Cells by Cell-Mediated Transmission

Shinsaku Sakurada,1,2,dagger Harutaka Katano,3,* Tetsutaro Sata,3 Hisashi Ohkuni,2 Toshiki Watanabe,1 and Shigeo Mori1

Department of Pathology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639,1 Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640,3 and Department of Immunology and Infectious Diseases, Institute of Gerontology, Nippon Medical School, Kawasaki 211-8533,2 Japan

Received 1 March 2001/Accepted 4 May 2001

Cell-free transmission of human herpesvirus 8 (HHV-8) to human cells in vitro has been reported to be difficult, if not impossible. The present experiments were conducted with the idea that cell-cell contact may produce much more effective transmission, so-called cell-mediated transmission. Primary human umbilical vein endothelial cells (HUVECs) were cocultured with an HHV-8-infected lymphoma cell line, BCBL-1 cells. When a ratio of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated BCBL-1 cells to HUVECs of 10:1 was used, more than 20% of HUVECs were found to express the HHV-8 latency-associated nuclear antigen (LANA) 48 h after the start of coculturing; this value increased to more than 30% after 72 h. HHV-8-encoded ORF26, K8, K8.1, K10, K11, ORF59, and ORF65 proteins were not detected in these HHV-8-infected HUVECs until 72 h. The HHV-8 antigens were not observed in HUVECs cocultured with TPA-treated BCBL-1 cells separated by a membrane. Thirty days after removal of the BCBL-1 cells from the cell-mediated transmission experiment, the HUVECs still expressed LANA and the HHV-8 genome was detected by PCR in these cells. Moreover, the ORF59 protein, a DNA replication-associated protein of HHV-8, was expressed in such HUVECs in the presence of TPA stimulation. These results indicated a far more effective transmission mechanism, cell-cell contact, suggesting the possibility that such a mechanism works in vivo.

* Corresponding author. Mailing address: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111, ext. 2627. Fax: 81-3-5285-1189. E-mail: katano{at}nih.go.jp.

dagger Present address: Bureau of International Cooperation, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

Journal of Virology, August 2001, p. 7717-7722, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7717-7722.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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