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Pathogenic Tick-Borne Virus Uses Host Neurons’ Transportation System to Move Its RNA

Flaviviruses are a significant threat to public health worldwide, and some infected patients develop severe, potentially fatal, neurological diseases. Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus, causes encephalic diseases resulting in photophobia, irritability, and sleep disorders. However, little is known about the pathogenic mechanisms and no effective treatment is available at present. A research team at Hokkaido University in Japan has previously showed that, in mouse neurons, genomic RNAs of TBEV are transported from the cell body to dendrites, the neuron's wire-like protrusions. Viral RNAs then reproduce viruses locally in dendrites disturbing normal neuronal activities. In the new study published online on August 28, 2017 in PNAS, the team looked into the transportation mechanism of viral RNAs in neurons, and discovered these RNAs make use of the cell's transportation system, which is normally used to move neuronal RNAs in dendrites. A specific non-coding sequence near the terminus of viral RNAs was found pivotal in interacting with the transportation system. When the sequence was mutated, the infected mouse showed reduced neurological symptoms. In the researchers’ biochemical experiments, viral RNAs could bind to a protein that forms a neuronal granule, which is part of the neuron's transportation system. Furthermore, their data shows that normal transportation of neuronal RNAs becomes affected by viral RNAs as a result of competition to use the transportation network. Associate Professor Kentaro Yoshii, who led the research team, commented "It is unprecedented for a neuropathogenic virus to hijack the neuronal granule system to transport their genomic RNA, which results in severe neurological diseases. The disruption of the neuronal granule system is also known to be involved in non-viral diseases such as Alzheimer's disease. So, the unique virus-host interaction we revealed should help us understand their pathogenesis and develop treatments in the future." The PNAS article is titled “Dendritic Transport of Tick-Borne Flavivirus RNA by Neuronal Granules Affects Development of Neurological Disease.”

[Press release] [PNAS abstract]