Deciphering cellular and transcriptional dynamics in dorsal root ganglia during temporal progression of herpes simplex virus infection: a single-cell RNA sequencing perspective
In herpes simplex virus (HSV) infections, the dynamic interplay between viral propagation and host immune responses is central to disease progression and resolution. This study leveraged single-cell RNA sequencing (scRNA-seq) to unveil the temporal cellular and molecular landscapes of dorsal root ganglia (DRG) following HSV infection in mice. As the infection evolved, a clear trend of M1 polarization was evident in macrophages, suggesting an initial pro-inflammatory immune response. Interestingly, the presence of NKT features and immune-related genes, such as gzmb, associated with the elimination of virus-infected cells, were predominantly observed on day 7 and peaked by day 14. Concurrently, neuronal damage indicators, specifically Atf3 expression, were localized in NP3 subtype neurons, implying a possible selective tropism of HSV towards this neuronal class. This infection-induced perturbation in NP3 neurons further instigated state or gene expression alterations in other neurons, particularly notable in abeta cells. A pseudotime trajectory analysis unveiled pivotal transcription factors, including Nfia and Pou2f1, orchestrating these cellular transitions, shedding light on potential regulatory nodes in HSV pathogenesis. Collectively, these findings provide novel insights into the cellular and transcriptional dynamics of DRG during HSV infection, offering potential therapeutic targets for intervention.