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

Pathogens elucidate two broad types of biochemical responses in the host. First is the activation of the host immune system. While the immune response is critical in combating pathogen infections, its over-activation often exacerbates tissue damage initiated by viral invasion [9, 10] . The second response is the up-regulation of host genes, such as protein biosynthetic pathways, that are crucial for sustaining pathogen invasion, replication and evasion [11] . Interestingly, genetically distinct respiratory viruses often modulate common host proteins and biological pathways during infection [1] . For example, many respiratory viruses trigger similar general airway inflammatory responses such as the expression of cytokines interleukin-6 (HUGO gene name IL6), interleukin-8 (IL8) and interleukin-11 (IL11), and granulocyte macrophage-colony stimulating factor (CSF2). These inflammatory responses in turn initiate IgA production, B cell differentiation and T cell stimulation [12] [13] [14] [15] [16] . As a consequence, diagnosis for specific viral infections is difficult since diverse respiratory viruses cause similar, often indistinguishable patient symptoms [1] . However, because distinct respiratory viruses converge on similar immune responses, opportunities also exist for targeting host proteins and pathways which will potentially affect multiple viral pathogens [17] . Moreover, human targets might be less susceptible to the evolution of drug resistance due to constraints on the virus to find alternative host pathways for its proliferation.