Brown Helen J, McBride William H, Zack Jerome A, Sun Ren
Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Antivir Ther. 2005;10(6):745-51.
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.
卡波西肉瘤相关疱疹病毒（KSHV）在淋巴细胞和内皮细胞中建立潜伏感染，且潜伏感染与肿瘤发生密切相关。由于在潜伏期间几乎没有病毒标志物表达，因此一直在寻找能够在体内安全有效地增加裂解基因表达的化合物。我们发现，非促肿瘤的佛波酯原卟啉素和蛋白酶体抑制剂硼替佐米在体外可诱导两种淋巴瘤细胞系中的KSHV立即早期、早期和晚期基因表达。它们诱导裂解基因表达的能力支持佛波酯和蛋白酶体调节的信号通路在KSHV激活中的作用，并促使对原卟啉素和硼替佐米作为KSHV相关恶性肿瘤治疗药物进行进一步研究。
