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 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.
Department of Microbiology, Osaka University Medical School, Suita, 565-0871, Osaka, Japan.
Ken
K
Nishimura
Keiji
K
Ueda
Shuhei
S
Sakakibara
Eunju
E
Do
Eriko
E
Ohsaki
Toshiomi
T
Okuno
Koichi
K
Yamanishi
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D012190:Retroviridae / Q000235:genetics; D013752:Tetracycline / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C116742:ORF 50 transactivator; D015534:Trans-Activators; D013752:Tetracycline