Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

Smith, Steven B.; Dampier, William; Tozeren, Aydin; Brown, James R.; Magid-Slav, Michal

Despite the diverse nature of the microarray data analyzed here, we found a large overlap between comparison groups in significant pathways, especially the immune system. Of the top twenty enriched pathways, eighteen are associated with immune response ( Table 2) . For example, EGFR signaling is known to be activated during infection by respiratory viruses FLU [36] and ENTERO [37, 38] . CD40 signaling is associated with CORON [39] , RSV [40] , and the general immune response [41] . Interferon gamma (IFNG) signaling is initiated by FLU [42] and RSV [43] , while interleukin 1 signaling is stimulated by FLU [42] . As components of the general immune response, interferon and interleukin pathways are activated by infectious agents such as hepatitis C virus (HCV), HIV and tuberculosis as well as chronic diseases like Crohn's disease, diabetes, and metastatic melanoma [44, 45] . The overall relationships between the transitory host immunity response launched by pathogenic infections versus that seen in chronic autoimmune and neurodegenerative diseases are complex and an intense area of investigation [46] . In addition, there are considerations about subtle shifts in gene function roles in different cell tissue types amongst the various diseases. Thus, we are cautious about any linkages between pathways involved in infections and those of chronic diseases as implied by our analysis without further validation studies.