Epstein-Barr Virus Infection at Single-Cell Resolution.

Epstein-Barr virus (EBV) infection has been studied at single-cell resolution for six decades and counting. Such investigations can reveal virus-host interactions and their dependence on viral strain, cellular niche, infection program, immune response regulation, and time. Understanding these factors is paramount to treating EBV-associated cancers and autoimmune diseases. This review examines the state of the field in EBV single-cell and spatial-omics spanning experimental models and clinical samples. Topics of primary interest include the growing adoption and emerging biological themes from single-cell assays and analyses, the shift from characterization toward functional single-cell studies, and strategies to maximize clinically relevant insights from dense single-cell and spatial datasets. Ancillary topics include the historical evolution of the single-cell EBV field and end-to-end single-cell sequencing workflows. Special attention is given to open questions in molecular mechanisms of EBV pathogenesis and how they might be resolved by future studies utilizing single-cell techniques.