Decoding host–pathogen interplay in EBV and KSHV oncogenesis toward precision therapies

Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are human oncogenic gammaherpesviruses that serve as paradigms for studying virus-induced malignancies. Over the past decades, research has uncovered the intricate ways persistent infection drives transformation and tumor development. Despite substantial progress, several fundamental questions remain unanswered. These include the molecular determinants regulating latency and lytic reactivation, the roles of viral non-coding RNAs, and the mechanisms of epigenetic and transcriptional reprogramming. Moreover, the interplay between viral infection and the tumor microenvironment—including immune evasion and inflammatory modulation—continues to present major challenges, particularly in understanding disease heterogeneity among virus-associated cancers. Recent studies employing multi-omics, spatial transcriptomics, and advanced model systems have revealed novel viral-host interactions but have also underscored the need for integrative approaches to reconcile cellular, molecular, and environmental contributors to tumorigenesis. What remains lacking is a comprehensive picture that unites these data into translational insights capable of informing therapeutic intervention.This Research Topic aims to elucidate the mechanisms underpinning KSHV- and EBV-associated oncogenesis by integrating molecular virology, tumor biology, and systems-level approaches. Central to this effort is the characterization of host-pathogen interactions that govern viral latency, reactivation, immune modulation, and tumor progression. The Research Topic seeks to identify key viral and host factors driving transformation, to uncover epigenetic and metabolic pathways commandeered during infection, and to define the contribution of the tumor microenvironment in sustaining malignant phenotypes. Insights derived from this work will not only enhance our understanding of viral oncogenesis but also enable the identification of therapeutic targets and predictive biomarkers for tailored interventions in EBV- and KSHV-associated diseases.This Research Topic encompasses basic, translational, and preclinical research aimed at deciphering host–virus interactions in EBV- and KSHV-associated oncogenesis. To gather further insights in these multidimensional virus–host systems, we welcome articles addressing, but not limited to, the following themes:o Latent and lytic reprogramming and their roles in tumor initiation, maintenance, and progressiono Oncogenic functions of viral proteins and viral non-coding RNAso Host epigenetic, transcriptional, and metabolic pathways hijacked by EBV and KSHVo Tumor microenvironment dynamics, inflammation, and immune escape mechanismso Multi-omics, single-cell, and spatial profiling approaches for functional dissection of viral oncogenesiso Development and application of in vitro and in vivo models—including cell lines, organoids, and humanized mice—for mechanistic and therapeutic studieso Translational strategies and novel targeted therapies for EBV- and KSHV-related malignanciesWe welcome Original Research, Reviews, Mini Reviews, and Perspectives that advance the understanding and clinical management of KSHV- and EBV-associated oncogenic diseases. Topic editors: Ling Ding, Shenyu Sun Source: https://www.frontiersin.org/research-topics/80757/decoding-host-pathogen-interplay-in-ebv-and-kshv-oncogenesis-toward-precision-therapies