Identification of core differentially expressed genes for respiratory syncytial virus infection.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

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