Effective human herpesvirus 8 infection of human umbilical vein endothelial cells by cell-mediated transmission.
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.
Sakurada
S
S
Department of Pathology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Katano
H
H
Sata
T
T
Ohkuni
H
H
Watanabe
T
T
Mori
S
S
D002450:Cell Communication; D004730:Endothelium, Vascular / Q000473:pathology / Q000821:virology*; D006566:Herpesviridae Infections / Q000473:pathology / Q000635:transmission / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions; D014779:Virus Replication