Viral latent proteins as targets for Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) induced lymphoma.

Michelle R Staudt, Dirk P Dittmer
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引用次数: 20

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is present in all Kaposi's sarcoma tumor cells as well as in several lymphomas that are linked to this agent. Every tumor cell expresses the viral latent protein LANA, which is required for KSHV latent replication and proper segregation of the viral episome. In certain tumors, other latent KSHV proteins (LANA-2/vIRF3, v-cyclin, v-IL6) are expressed as well. Since all herpesviruses persist for life in infected individuals, only eradication of latent virus can cure infection. The KSHV latent genes serve as bona fide tumor markers, but do they also provide targets for anti-tumor and/or anti-viral drugs? To decide this question we review the known biochemical interactions between KSHV latent proteins and their viral and cellular partners. Recent epidemiological studies show that KSHV lytic replication precedes KSHV associated cancers. Gancilovir has been linked to KS tumor regression, which implicates the KSHV-encoded polymerase as a potential intervention point. Yet, KSHV specific transactivators might represent more specific targets, as they have no cellular homologs. In particular Rta/orf50 is necessary and sufficient for lytic replication and deserves serious consideration as a target for KSHV-specific antivirals.

病毒潜伏蛋白作为卡波西肉瘤和卡波西肉瘤相关疱疹病毒(KSHV/HHV-8)诱导淋巴瘤的靶点
卡波西氏肉瘤相关疱疹病毒(KSHV/HHV-8)存在于所有卡波西氏肉瘤肿瘤细胞以及与该制剂相关的几种淋巴瘤中。每个肿瘤细胞都表达病毒潜伏蛋白LANA,这是KSHV潜伏复制和病毒片段适当分离所必需的。在某些肿瘤中,其他潜伏的KSHV蛋白(LANA-2/vIRF3, v-cyclin, v-IL6)也表达。由于所有疱疹病毒在感染个体中持续存在,只有根除潜伏病毒才能治愈感染。KSHV潜伏基因作为真正的肿瘤标志物,但它们是否也提供抗肿瘤和/或抗病毒药物的靶标?为了解决这个问题,我们回顾了已知的KSHV潜伏蛋白与其病毒和细胞伙伴之间的生化相互作用。最近的流行病学研究表明,KSHV裂解复制先于KSHV相关的癌症。更西洛韦与KS肿瘤消退有关,这意味着kshv编码聚合酶是一个潜在的干预点。然而,KSHV特异性反激活因子可能代表更特定的靶标,因为它们没有细胞同源物。特别是Rta/orf50对于裂解复制是必要和充分的,值得认真考虑作为kshv特异性抗病毒药物的靶标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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