Network Medicine Approach to Viral Infections: Unraveling Universal and Virus-Specific Immune Pathways

Viral infections continue to pose significant global health challenges, with pathogens like Dengue Virus (DENV), Chikungunya Virus (CHIKV), Yellow Fever Virus (YFV), Human Immunodeficiency Virus (HIV), and Influenza Virus (FLU) contributing to widespread morbidity and mortality. A comprehensive understanding of the host immune response to these infections is crucial for developing more effective diagnostics, treatments, and vaccines. In this study, we conducted a meta-analysis of transcriptomic datasets from whole blood and peripheral blood mononuclear cell (PBMC) samples of individuals infected with DENV, CHIKV, YFV, HIV, and FLU. Utilizing a systems biology approach, we identified both shared and virus-specific molecular mechanisms underlying immune responses to these infections. Several key genes, including OAS2, MX1, and IFI44L, were consistently up-regulated across multiple viral infections, highlighting their roles in antiviral defense, immune modulation, and cellular stress responses. Additionally, virus-specific genes such as TNFSF10 and NT5C3A were found to be uniquely up-regulated in arboviruses, underscoring the distinct immune pathways activated by different viral families. Our co-expression network analysis revealed coordinated gene expression patterns across different viral infections, offering insights into conserved molecular networks that could inform the development of broad-spectrum antiviral therapies. Despite challenges related to biological heterogeneity and variations in study design, this meta-analysis provides a foundation for future research aimed at unraveling the complex immune mechanisms that govern host-pathogen interactions.