Andrei Graciela, Snoeck Robert
Laboratory of Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
Curr Opin Infect Dis. 2015 Dec;28(6):611-24. doi: 10.1097/QCO.0000000000000213.
To discuss the role of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication in viral-associated diseases and assess the progress on targeting KSHV lytic replication as a strategy to prevent KSHV-related malignancies.
New inhibitors of viral lytic replication are being developed as well as novel modalities are being investigated to target cellular processes that the virus hijacks during its life cycle. Research has also focused on reactivating viral lytic replication in latently infected tumour cells (lytic induction therapy) to promote death of tumour cells.
KSHV is linked to three malignancies: Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Despite significant progress in understanding KSHV pathobiology, no therapeutic guidelines for the management of KSHV-related diseases exist, and current treatments are suboptimal and associated with toxicity. Antiherpesvirus drugs have shown inconsistent results in KSHV-associated malignancies that harbour the virus in a latent state. However, lytic replication plays a crucial role in the process of tumorigenesis. Therefore, not only antiviral agents directed against the virus replicative cycle but also agents that target cellular processes that are activated by the virus are being investigated. Antivirals may also be used in combination with inducers of the viral lytic stage.
探讨卡波西肉瘤相关疱疹病毒（KSHV）裂解复制在病毒相关疾病中的作用，并评估将靶向KSHV裂解复制作为预防KSHV相关恶性肿瘤策略的进展。
正在研发新的病毒裂解复制抑制剂，并研究针对病毒在其生命周期中劫持的细胞过程的新方法。研究还集中于在潜伏感染的肿瘤细胞中重新激活病毒裂解复制（裂解诱导疗法）以促进肿瘤细胞死亡。
KSHV与三种恶性肿瘤相关：卡波西肉瘤、原发性渗出性淋巴瘤和多中心Castleman病。尽管在理解KSHV病理生物学方面取得了重大进展，但尚无KSHV相关疾病管理的治疗指南，目前的治疗效果欠佳且伴有毒性。抗疱疹病毒药物在潜伏感染病毒的KSHV相关恶性肿瘤中的疗效不一。然而，裂解复制在肿瘤发生过程中起关键作用。因此，不仅正在研究针对病毒复制周期的抗病毒药物，还在研究针对被病毒激活的细胞过程的药物。抗病毒药物也可与病毒裂解阶段的诱导剂联合使用。
