Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.

Infectious diseases are a persistent threat throughout the twenty-first century, owing to their widespread transmission mediated by global connectivity. Benefiting from the advancement of eukaryotic, prokaryotic (e.g., MATQ-seq and BacDrop), and dual (e.g., PatH-Cap) single-cell sequencing technologies, changes in each side and host-pathogen interactions can be elucidated. Pathogens undergo adaptive evolution in the host microenvironment, exhibiting different transcription profiles (e.g., upregulated HSV-1 immediate-early genes during infection), transcription efficiencies, and others. Consequently, they develop distinct replication capacity, virulence, and other phenotypes. For the host, intrinsic differences among cells and variations brought by diverse phenotypic pathogens together determine the heterogeneity of its responses (e.g., the dual roles of interferon-I at different infection stages). Interferon-related pathway alterations (influencing both adaptive and innate immune responses) and cell exhaustion (manifesting as the functional impairment of cells) are observed in various infections, seemingly as a shared approach in host-pathogen interactions. These underlying commonalities provide a basis for the development of broad-spectrum therapeutic targets. Collectively, this work reviewed recent progress of single-cell sequencing technologies and their applications in infectious diseases, aiming to facilitate the development of powerful diagnostic or therapeutic strategies and thus advance precision medicine.