Prostratin and bortezomib are novel inducers of latent Kaposi's sarcoma-associated herpesvirus.
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent infections in lymphocytes and endothelial cells, and latent infection is closely linked to tumorigenesis. As few viral markers are expressed during latency, compounds that can safely and efficiently increase lytic gene expression in vivo have been sought. We have found that the non-tumour-promoting phorbol ester prostratin and the proteasome inhibitor bortezomib induce immediate-early, early and late KSHV gene expression from two lymphoma cell lines in vitro. Their ability to induce lytic gene expression supports a role for phorbol-ester and proteasome-regulated signalling pathways in KSHV reactivation and prompts further investigation of prostratin and bortezomib as therapeutic agents for KSHV-associated malignancies.
Brown
Helen J
HJ
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA.
McBride
William H
WH
Zack
Jerome A
JA
Sun
Ren
R
D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency
D001897:Boronic Acids; D017874:Immediate-Early Proteins; D010703:Phorbol Esters; D011480:Protease Inhibitors; D011719:Pyrazines; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins; C070999:prostratin; D000069286:Bortezomib