Project Summary/Abstract Metabolic reprograming has been readily recognized as the hallmark of cancer. Specifically, three- dimensional (3D) cell system is well documented to regain intrinsic metabolic properties and to better mimic the in vivo situation than two-dimensional (2D) cell system. We have shown that Kaposi’s sarcoma-associated herpesvirus (KSHV), an etiological agent of Kaposi’s sarcoma (KS) and pleural effusion lymphoma, specifically alters host spermidine and proline syntheses in a 3D-dependent manner, contributing to the LANA-mediated latent episomal maintenance for viral persistency and oncogenesis, which is a crux of this application. As this KSHV-mediated spermidine and proline biosynthesis reprograming is also shared by most non-viral cancers, this study will contribute to understanding general cancer metabolic reprograming.