Ras signalling in infectious disease pathology: Mechanisms, tissue damage, and clinical implications

Ras signalling is an important regulator of cell proliferation, survival, differentiation, and immune responses. Although Ras pathways have been extensively studied in cancer biology, increasing evidence suggests that many pathogens also manipulate Ras-associated signalling networks to support infection, persistence, and immune evasion. Viruses, bacteria, and parasites can alter Ras activity either directly or indirectly through downstream pathways such as MAPK/ERK and PI3K/AKT. However, activation of ERK or AKT does not always indicate direct Ras involvement, and this distinction remains important in infectious disease research. Recent studies show that pathogens including SARS-CoV-2, Epstein-Barr virus, hepatitis B virus, Helicobacter pylori, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Leishmania species regulate Ras-associated signalling in ways that contribute not only to pathogen survival but also to inflammation, tissue injury, and disease progression. In several infections, isoform-specific regulation of H-Ras, K-Ras, and N-Ras has also been observed, suggesting distinct roles in immune modulation and pathological outcomes. Dysregulated Ras-associated signalling has been linked to lung injury, liver fibrosis, gastric epithelial damage, granuloma formation, and systemic dissemination of infection. This review summarizes current evidence on the role of Ras signalling in infectious disease pathology, focusing on host-pathogen interactions, isoform-specific regulation, tissue damage, and therapeutic implications. Although Ras signalling represents a promising host-directed target, much of the current evidence remains indirect and requires further pathogen-specific validation.