Deciphering viral infections at single-cell resolution: From immune dynamics to host-pathogen interactions

Single-cell RNA sequencing (scRNA-seq) has emerged as a transformative technology in infectious disease research, enabling high-resolution characterization of cellular heterogeneity, immune dynamics, and host-pathogen interactions at the single-cell level. In the context of viral infections-including SARS-CoV-2, hepatitis B virus (HBV), human immunodeficiency virus (HIV), influenza virus, and respiratory syncytial virus (RSV)-scRNA-seq has provided critical insights into immune-cell heterogeneity, immune landscape remodeling, and the emergence of previously unrecognized cellular states. Beyond immune profiling, scRNA-seq enables direct detection of viral transcripts within infected cells. This allows discrimination between productively infected and bystander cells and reveals virus-induced transcriptional reprogramming within target tissues. Additionally, single-cell approaches facilitate the analysis of adaptive immune repertoires through integrated integrated T-cell receptor (TCR) and B-cell receptor (BCR) sequencing sequencing and uncover intra-host viral diversity and evolutionary dynamics at unprecedented resolution. This review summarizes recent advances in the application of scRNA-seq in viral infection research, with a focus on immune regulation, host-pathogen co-transcriptomics, inflammatory signaling pathways, biomarker discovery, and translational implications. Comparative single-cell studies across acute and chronic viral infections have further revealed both shared antiviral programs and virus-specific immune adaptations.We further discuss current technical limitations and emerging computational strategies, as well as future integration with spatial transcriptomics and multi-omics platforms. Collectively, these developments highlight the potential of single-cell technologies to advance mechanistic understanding and guide precision diagnostics and therapeutic strategies in viral diseases.