Advances in KSHV Research: Molecular Pathogenesis, Immune Evasion, and Evolving Therapeutic Horizon

ABSTRACT Kaposi's sarcoma–associated herpesvirus (KSHV/HHV‐8) infects more than 140 million people worldwide, with transmission occurring mainly through saliva, blood transfusion, and sexual contact. Despite its global burden, especially in HIV‐endemic regions, KSHV‐related diseases remain underdiagnosed and poorly managed. This review highlights current knowledge of KSHV pathogenesis with emphasis on latency, immune evasion, and oncogenesis. We summarize how viral proteins such as latency‐associated nuclear antigen (LANA) and viral interleukin‐6 (vIL‐6) manipulate host cell survival pathways, including PI3‐K signaling and Rho GTPase regulation, to drive Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Advances in diagnostics (PCR, serology, immunohistochemistry) and targeted therapies, particularly rituximab, have improved patient outcomes, although treatment challenges remain. Ongoing efforts in vaccine development and immune‐based interventions hold promise for controlling viral persistence and preventing cancer progression. A deeper understanding of KSHV–host interactions will be crucial for designing next‐generation therapies and guiding future public health strategies. This review is framed as an update on recent advances in KSHV biology and therapeutic research. We distinguish between well‐established mechanisms and emerging hypotheses, highlighting how new discoveries in viral pathogenesis and host–virus interactions are reshaping potential therapeutic strategies.