Abstract
Genital herpes (GH), which is primarily caused by herpes simplex virus type 2 (HSV‑2), is the leading cause of genital ulcers worldwide, and is characterized by recurring outbreaks of painful genital lesions. Despite the high prevalence of GH, the metabolic and transcriptomic mechanisms underlying disease recurrence remain poorly understood. Therefore, the present study aimed to identify metabolic alterations in patients with HSV‑2 GH via integrating transcriptomics, metabolomics and single‑cell RNA‑sequencing (scRNA‑seq) analyses. Non‑targeted metabolomics identified significant changes in pathways associated with glycerophospholipid metabolism, amino acid biosynthesis and cholesterol metabolism. In addition, RNA‑seq analysis revealed that genes associated with the alanine, aspartate and glutamate, and valine, leucine and isoleucine metabolism pathways were significantly upregulated in patients with recurrent HSV‑2 GH. Furthermore, scRNA‑seq data showed that IDH1 and ETNK1 were upregulated, mainly in dendritic cells (DCs), plasmacytoid DCs and monocytes derived from patients with GH. Notably, the expression levels of genes associated with oxidative phosphorylation, such as MT‑CYB and MT‑CO3, were significantly elevated across monocytes, T cells and B cells. Overall, the results of the current study suggested that metabolic reprogramming could occur in patients with recurrent HSV‑2 GH, thus providing potential biomarkers and therapeutic targets that could be involved in the future development of treatment approaches.