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​Beckham lab discovers that alpha-synuclein, the protein that causes Parkinson’s disease, functions as a neuron-specific restriction factor to inhibit viral infections in the brain.

Following viral infection of neurons, alpha-synuclein protein expression is increased in primary neuron cultures. Virus-induced alpha-synuclein localizes with virus proteins and with the endoplasmic reticulum (ER)-associated protein, Rab1, in neurons. In a mouse model of viral encephalitis with West Nile virus, mice lacking the gene for alpha-synuclein (knockout mice) are completely normal until challenged by viral infection. Upon viral challenge, alpha-synuclein knockout mice exhibit marked increase in viral growth, neuronal death, disease and mortality compared to control mice. Following viral infection of knockout mice, there are no differences in interferon responses or CD3+ Tcell responses to viral infection. However, alpha-synuclein knockout primary neurons exhibit robust changes in endoplasmic reticulum (ER) stress responses. Specific changes ER stress signaling are important in the pathogenesis of viral infections in neurons and play a role in virus-induced cell death.

Thus, we conclude that alpha-synuclein functions as a novel restriction factor in the central nervous system by localizing to virus-induced membranes and altering ER-associated signaling and inhibiting viral growth in neurons. These data were recently accepted for publication in the Journal of Virology (PMID: 26719256).


This work was completed by Erica Beatman, Aaron Massey and Katie Shives in the Beckham lab. Alphavirus experiments were completed in collaboration with the Tem Morrison laboratory and Kristina Burrack in the Department of Immunology and Microbiology at the University of Colorado Anschutz Medical Campus.