Single-cell RNA sequencing offers novel perspectives in viral infection research

The global emergence of multiple viral zoonoses underscores the substantial threats of viral infections to human health. Given the dynamic and complex mechanisms underlying viral pathogenesis, sophisticated approaches are requisite to advance viral research. Here, we present a systematic review of single-cell RNA sequencing (scRNA-seq), a high-throughput technology enabling transcriptomic profiling at the individual cell level, focusing on its pivotal role in elucidating heterogeneous host cellular responses to viral infection and deciphering underlying pathogenic mechanisms. We summarize scRNA-seq’s developmental milestones, compare characteristics of various platforms, and outline its key applications in viral infection research: identifying infection-induced novel cell types/subpopulations, characterizing virus-specific host cell gene expression changes, defining viral target cells, elucidating antiviral immune mechanisms, and clarifying in vivo viral distribution and pathogenesis. By synthesizing these information, this review offers novel research and technical perspectives for dissecting the dynamic and complex virus-host interactions, aiding future advancements in viral infection research.