세미나

Oncogenic γ-herpesviruses such as Kaposi’s sarcoma-associated herpesvirus (KSHV) exploit host metabolic pathways to support persistent infection, episodic reactivation, and ultimately the malignant transformation of infected cells. Using 3D spheroid cultures that better mimic the in vivo metabolic environment, we performed metabolomic analyses and observed marked increases in proline and spermidine levels. Mechanistic studies based on these findings revealed that KSHV reprograms proline biosynthesis through activation of pyrroline-5-carboxylate reductase (PYCR) by the viral K1 oncoprotein. This interaction elevates intracellular proline levels, thereby promoting three-dimensional spheroid growth and tumorigenesis in vivo. More recently, we further demonstrated that KSHV infection enhances spermidine synthesis and consequently increases eIF5A hypusination, which stabilizes latent nuclear antigen (LANA) expression essential for episome maintenance during latency. Collectively, these studies highlight a multi-layered metabolic hijacking strategy in which KSHV first amplifies amino acid anabolic pathways to drive viral transformation and then engages the polyamine–hypusination axis to sustain viral latency and long-term persistence.