A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus (KSHV) induces apoptosis, which is blocked in KSHV-infected cells

Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50, is expressed in the immediate-early phase of reactivation and plays a critical role in inducing the viral lytic cycle in KSHV-infected cells. We established cel...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2003-11, Vol.316 (1), p.64-74
Main Authors: Nishimura, Ken, Ueda, Keiji, Sakakibara, Shuhei, Do, Eunju, Ohsaki, Eriko, Okuno, Toshiomi, Yamanishi, Koichi
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell death
Cell Line
Gene Expression Regulation, Viral
Herpesvirus 8, Human - genetics
Herpesvirus 8, Human - pathogenicity
Herpesvirus 8, Human - physiology
Human herpesvirus 8
Humans
KSHV/RTA
Mice
NIH 3T3 Cells
Retroviridae - genetics
RTA protein
Tet-Off
Tetracycline - pharmacology
Trans-Activators - genetics
Trans-Activators - metabolism
Virus Replication
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Summary:Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50, is expressed in the immediate-early phase of reactivation and plays a critical role in inducing the viral lytic cycle in KSHV-infected cells. We established cell clones from BJAB cells and replication-deficient BCBL-1 cells in which KSHV RTA expression was controlled by an inducible promoter of the tetracycline-based Tet-Off expression system. In RTA-inducible BJAB cells, tetracycline removal induced the synthesis of RTA, resulting in cell death. DNA fragmentation, structural changes in the cell membrane, and poly(ADP-ribose) polymerase (PARP) cleavage were observed in the RTA-induced BJAB cells, indicating that RTA expression induced caspase activation and cell death by apoptosis. However, expression of RTA in RTA-inducible BCBL-1 cells did not undergo apoptosis and cell death. These results suggested that KSHV RTA is an apoptosis inducer that is opposed by an antiapoptotic pathway in infected cells.
ISSN:0042-6822
1096-0341
DOI:10.1016/S0042-6822(03)00582-8