通过针对 KSHV 持续合成蛋白 PF-8 的基本活性来抑制 KSHV 复制。
Inhibiting KSHV replication by targeting the essential activities of KSHV processivity protein, PF-8.
发表日期:2024 Oct
作者:
Jennifer Kneas Travis, Lindsey M Costantini
来源:
JOURNAL OF MEDICAL VIROLOGY
摘要:
卡波西肉瘤疱疹病毒 (KSHV) 是多种人类疾病的病原体。 KSHV 感染无法治愈。 KSHV 建立双相终身感染。在裂解阶段,新基因组由七种病毒 DNA 复制蛋白复制。持续合成因子 (PF-8) 的功能是将 DNA 聚合酶束缚在 DNA 上,从而有效合成新的病毒基因组。 PF-8 自缔合,与 KSHV DNA 复制蛋白和病毒 DNA 相互作用。抑制病毒 DNA 复制将减少宿主内的感染并减少向新个体的传播。在这篇综述中,我们总结了 PF-8 分子和结构研究,详细介绍了有效裂解 DNA 复制所需的基本蛋白质-蛋白质和核酸相互作用,确定了未来的研究领域,并提出 PF-8 作为有前途的抗病毒靶点。此外,我们还讨论了 Epstein-Barr 病毒的持续合成因子与 PF-8 的相似之处,这可以促进泛疱疹病毒抗病毒治疗靶向策略。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。
Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of several human diseases. There are no cures for KSHV infection. KSHV establishes biphasic lifelong infections. During the lytic phase, new genomes are replicated by seven viral DNA replication proteins. The processivity factor's (PF-8) functions to tether DNA polymerase to DNA, so new viral genomes are efficiently synthesized. PF-8 self-associates, interacts with KSHV DNA replication proteins and the viral DNA. Inhibition of viral DNA replication would diminish the infection within a host and reduce transmission to new individuals. In this review we summarize PF-8 molecular and structural studies, detail the essential protein-protein and nucleic acid interactions needed for efficient lytic DNA replication, identify future areas for investigation and propose PF-8 as a promising antiviral target. Additionally, we discuss similarities that the processivity factor from Epstein-Barr virus shares with PF-8, which could promote a pan-herpesvirus antiviral therapeutic targeting strategy.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.