Associative study of human herpesvirus 8 and Kaposi's sarcoma: Mapping viral oncogenic properties and the clinical scenario in oncological patients.

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.