Klass Carmen Manuela, Offermann Margaret K
Winship Cancer Institute, Emory University, 1365-B Clifton Road NE, Atlanta, GA 30322, USA.
Curr Opin Oncol. 2005 Sep;17(5):447-55. doi: 10.1097/01.cco.0000172823.01190.6c.
Human herpesvirus-8, also called the Kaposi's sarcoma herpesvirus, is present in all cases of Kaposi's sarcoma and primary effusion lymphoma and in some cases of multicentric Castleman's disease. This review discusses mechanisms by which human herpesvirus-8 contributes to tumorigenesis and how this knowledge can be used to target the virus for the treatment of these tumors.
Most primary effusion lymphomas and Kaposi's sarcoma tumor cells are latently infected with human herpesvirus-8 and hence resistant to antiherpesvirus drugs that are dependent on lytic replication. In contrast, many of the cells infected with human herpesvirus-8 in multicentric Castleman's disease support lytic replication, so that clinical improvement frequently occurs in response to treatment with antiherpesvirus drugs. The resistance of latently-infected tumor cells to antiherpesvirus drugs can be overcome by inducing human herpesvirus-8 to reenter the lytic cascade in the presence of antiherpesvirus drugs. This leads to apoptosis of virally infected cells without increasing production of infectious virus. Alternatively, the replication and maintenance of the human herpesvirus-8 episome during latency can be disrupted by glycyrrhizic acid or hydroxyurea so that the virus no longer contributes to tumorigenesis. Both the innate and acquired immune systems can also be augmented to help prevent or treat human herpesvirus-8-associated tumors.
Novel strategies targeting human herpesvirus-8, which is present in all cases of Kaposi's sarcoma and primary effusion lymphoma, provide opportunities for selectively killing tumor cells.
人类疱疹病毒8型，也称为卡波西肉瘤疱疹病毒，存在于所有卡波西肉瘤、原发性渗出性淋巴瘤病例以及某些多中心Castleman病病例中。本综述讨论了人类疱疹病毒8型促成肿瘤发生的机制，以及如何利用这些知识针对该病毒来治疗这些肿瘤。
大多数原发性渗出性淋巴瘤和卡波西肉瘤肿瘤细胞都潜伏感染了人类疱疹病毒8型，因此对依赖裂解复制的抗疱疹病毒药物具有抗性。相比之下，多中心Castleman病中许多感染人类疱疹病毒8型的细胞支持裂解复制，所以使用抗疱疹病毒药物治疗后临床症状常常会改善。在抗疱疹病毒药物存在的情况下，通过诱导人类疱疹病毒8型重新进入裂解级联反应，可以克服潜伏感染肿瘤细胞对抗疱疹病毒药物的抗性。这会导致病毒感染细胞凋亡，而不会增加传染性病毒的产生。或者，甘草酸或羟基脲可以破坏人类疱疹病毒8型在潜伏期间附加体的复制和维持，从而使该病毒不再促成肿瘤发生。先天性和获得性免疫系统也可以得到增强，以帮助预防或治疗与人类疱疹病毒8型相关的肿瘤。
针对存在于所有卡波西肉瘤和原发性渗出性淋巴瘤病例中的人类疱疹病毒8型的新策略，为选择性杀死肿瘤细胞提供了机会。
