Identification of core differentially expressed genes for respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a highly contagious pathogen and the predominant cause of upper and lower respiratory tract infections. RSV-specific antiviral drugs are at an early stage, and clinical and experimental therapies targeting pathogenesis and immune pathways are limited, with challenging application.

We systematically analyzed blood transcriptome data from 92 RSV patients and 47 healthy controls. Key functional genes were identified via differential expression analysis, weighted gene co-expression network analysis (WGCNA), core module identification, machine learning, protein-protein interaction (PPI) network analysis, and co-localization mapping. An independent cohort (28 patients, 8 controls) was used for validation. Immune-cell infiltration patterns influenced by key genes were assessed, and therapeutic targets were predicted. Quantitative real-time PCR (qRT-PCR) on clinical blood samples validated disease-associated core genes.

We identified eight functionally critical feature genes; seven (IL1RN, RETN, GPR141, ARG1, SQRDL, SAMSN1, and MMP8) were significantly upregulated (FDR < 0.01), while only CD96 was downregulated. Immune-infiltration analysis showed a strikingly consistent association between these key genes and immune cells, except for CD96. Notably, ARG1 and RETN shared a causal variant linked to lower respiratory tract infection pathology. Five candidate compounds with inverse regulatory effects on feature gene expression were predicted. qRT-PCR results validated RETN as the most critical core gene associated with RSV infection.

This study systematically screened potential key genes via integrated bioinformatics and molecular validation, and identified RETN as a potential therapeutic target for RSV disease.