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.
Nishimura
Ken
K
Department of Microbiology, Osaka University Medical School, Suita, 565-0871, Osaka, Japan.
Ueda
Keiji
K
Sakakibara
Shuhei
S
Do
Eunju
E
Ohsaki
Eriko
E
Okuno
Toshiomi
T
Yamanishi
Koichi
K
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