da Silva João Vitor Geisteira Oliveira, Vieira Jessica Manya Bittencourt Dias, de Oliveira Santos Eidy
Programa de Pós-Graduação Em Biomedicina Translacional (BIOTRANS), Rio de Janeiro, RJ, Brazil.
Universidade Do Estado Do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil.
Immunol Res. 2025 Sep 20;73(1):136. doi: 10.1007/s12026-025-09684-9.
Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiological agent of Kaposi's Sarcoma (KS) and other lymphoproliferative disorders. Over three decades after its discovery, many aspects of its biology, latency, immune evasion, and oncogenic mechanisms remain poorly understood. This review provides an integrative and up-to-date analysis of KSHV, from its molecular architecture and gene regulation to its complex host interactions and transmission dynamics. We highlight key viral proteins-LANA, RTA, vFLIP, vCyc, kaposins, and viral miRNAs-that orchestrate latency maintenance, lytic reactivation, immune modulation, and tumor development. The review maps how KSHV establishes persistent infection, exploits host signaling pathways, and induces hallmarks of cancer, such as angiogenesis and uncontrolled proliferation. We also discuss glycoprotein-receptor interactions involved in viral entry and the structural mechanisms facilitating KSHV-cell fusion. Clinically, we present updated epidemiological data and analyze the diversity of KS forms-classic, endemic, iatrogenic, epidemic, and anaplastic-highlighting regional disparities, diagnostic challenges, and treatment gaps. The article emphasizes the virus's role in aggressive neoplasms in immunocompromised individuals and underscores the lack of antiviral strategies specifically targeting KSHV. By combining molecular virology, oncogenesis, immunology, and epidemiology, this review advances the current understanding of KSHV and reinforces the urgent need for effective diagnostic tools, preventive strategies, and targeted therapies. Our findings contribute to bridging knowledge gaps and promoting translational approaches to mitigate the global impact of KSHV-related diseases.
人类疱疹病毒8型（HHV - 8），也称为卡波西肉瘤相关疱疹病毒（KSHV），是卡波西肉瘤（KS）和其他淋巴增殖性疾病的病原体。在其被发现三十多年后，其生物学、潜伏、免疫逃逸和致癌机制的许多方面仍知之甚少。本综述对KSHV进行了全面且最新的分析，涵盖从其分子结构和基因调控到复杂的宿主相互作用及传播动态。我们重点介绍了关键病毒蛋白——LANA、RTA、vFLIP、vCyc、卡波西蛋白和病毒微小RNA——它们协调潜伏维持、裂解再激活、免疫调节和肿瘤发展。该综述描绘了KSHV如何建立持续感染、利用宿主信号通路并诱导癌症特征，如血管生成和不受控制的增殖。我们还讨论了参与病毒进入的糖蛋白 - 受体相互作用以及促进KSHV - 细胞融合的结构机制。在临床方面，我们呈现了最新的流行病学数据，并分析了KS形式的多样性——经典型、地方性、医源性、流行性和间变性——突出区域差异、诊断挑战和治疗差距。文章强调了该病毒在免疫功能低下个体侵袭性肿瘤中的作用，并强调缺乏专门针对KSHV的抗病毒策略。通过结合分子病毒学、肿瘤发生学、免疫学和流行病学，本综述推进了当前对KSHV的理解，并强化了对有效诊断工具、预防策略和靶向治疗的迫切需求。我们的研究结果有助于弥合知识差距，并促进转化方法以减轻KSHV相关疾病的全球影响。
