Approximately 15–20% of cancers are caused by viruses. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is an oncogenic virus that is the etiologic agent of not only Kaposi sarcoma but also the lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV can infect a broad tropism of cells, including B lymphocytes, wherein KSHV encodes specific viral proteins that can transform the cell. KSHV infection precedes the progression of PEL and MCD. KSHV establishes lifelong infection and has two phases of its lifecycle: latent and lytic. During the latent phase, viral genomes are maintained episomally with limited gene expression. Upon sporadic reactivation, the virus enters its replicative lytic phase to produce infectious virions. KSHV relies on its viral products to modulate host factors to evade immune detection or to co-opt their function for KSHV persistence. These manipulations dysregulate normal cell pathways to ensure cell survival and inhibit antiviral immune responses, which in turn, contribute to KSHV-associated malignancies. Here, we highlight the known molecular mechanisms of KSHV that promote lymphomagenesis and how these findings identify potential therapeutic targets for KSHV-associated lymphomas.
约15-20%的癌症由病毒引起。卡波西肉瘤相关疱疹病毒（KSHV），亦称为人类疱疹病毒8型（HHV8），是一种致癌病毒，不仅是卡波西肉瘤的病原体，也是淋巴组织增生性疾病——原发性渗出性淋巴瘤（PEL）和多中心性卡斯尔曼病（MCD）的致病因子。KSHV可感染多种类型的细胞，包括B淋巴细胞，并通过编码特异性病毒蛋白实现细胞转化。KSHV感染是PEL和MCD疾病进展的前提条件。该病毒可建立终身感染，其生命周期包含潜伏期和裂解期两个阶段。在潜伏期，病毒基因组以附加体形式存在，基因表达受限；当病毒被偶发性激活后，则进入复制性裂解期以产生具有感染性的病毒颗粒。KSHV依赖其病毒产物调控宿主因子，从而逃避免疫识别或利用宿主功能维持自身持续感染。这些调控机制会破坏正常细胞通路，确保细胞存活并抑制抗病毒免疫反应，最终促进KSHV相关恶性肿瘤的发生。本文重点阐述KSHV促进淋巴瘤发生的已知分子机制，并探讨这些发现如何为KSHV相关淋巴瘤的治疗靶点识别提供依据。
Molecular Mechanisms of Kaposi Sarcoma-Associated Herpesvirus (HHV8)-Related Lymphomagenesis
肿瘤(癌症)患者之家