Alvarez-Kuglen, M. | bioRxiv Science

bioRxiv2025

Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence

Kaposis sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1--genetically or pharmacologically--leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.

molecular biology↗

bioRxiv2022

Microscopic Imaging of Epigenetic Age

Biomarkers of biological age that predict the risk of disease and expected lifespan better than chronological age are key to efficient and cost-effective healthcare1-3. To advance a personalized approach to healthcare, such biomarkers must perform on the individual rather than population level, demonstrate single cell resolution, and provide scalable and cost-effective measurements. We developed a novel approach - image-based chromatin and epigenetic age (ImAge), that utilizes image texture features based on the patterns of chromatin and epigenetic marks in single nuclei. We observed the emergence of intrinsic trajectories of ImAge using dimensionality reduction without regression on chronological age. ImAge was correlated with chronological age in all tissues and organs examined and was consistent with the expected acceleration and/or deceleration of biological age in chronologically identical mice treated with chemotherapy or following a caloric restriction regimen, respectively. ImAge from chronologically identical mice inversely correlated with their locomotor activity (greater activity for younger ImAge), consistent with the essential role of locomotion as an aging biomarker. Finally, we demonstrated that ImAge is reduced upon partial reprogramming in vivo following transient expression of OSKM cassette in the liver and skeletal muscles of old mice and validated the power of ImAge to assess the heterogeneity of reprogramming. We propose that ImAge represents the first-in-class individual-level biomarker of aging and rejuvenation with single-cell resolution.

systems biology↗