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

The Parkin-UPS pathway is not commonly associated with general immune response to viral infection. However, other ubiquitylation proteins, such as ISG15, are known to play roles in host defense [55, 56] . Associations between influenza infection and neuroinflammation in early onset autosomal recessive Parkinson's disease have been recently suggested [57] [58] [59] . At least one factor in the progression of Parkinson's disease is the formation of neuotoxic Lewy bodies due to increases in SNCA. Increases in SNCA are believed to be the result of loss-of-function mutations in PARK2 which cause disruptions in the protein's localization and solubility [60] [61] [62] . Polymorphisms in the gene PARK2 have also been associated with susceptibility to infectious diseases such as leprosy, typhoid fever and paratyphoid fever, although the exact mechanism is still unclear [63, 64] . Jang et al. observed activation of SNCA in mouse nervous tissue long after pathogenic H5N1 FLU infection where the increased levels of SNCA mirror those found in Parkinson's disease [57] . Similarly, recent findings from Rohn and Catlin indicate FLU as a potential causative factor for Parkinson's disease [58] . Indeed, links between FLU and other neurodegenerative diseases have been suggested, and these include seizures, transverse myelitis, expressive aphasia, syncope, encephalitis, neuromyelitis optica, and central nervous system disease in general [65] [66] [67] . PARK2 itself has a low signal at the mRNA level which might be due to its significant regulation by post-translation processes [52, 54] . Further studies are needed to determine the mechanism