Virus hijacks neuronal granule system to transport genomic content

Flavivirus is a genus of viruses within the family Flaviviridae, which includes – but is not limited to – the West Nile virus and the tick-borne encephalitis virus (TBEV). These flaviviruses are known to cause encephalic disease and in the case of TBEV, the following neurological manifestations can arise: photophobia, irritability and sleep disorders.

Previous research from a team at Hokkaido University (Sapporo, Japan) revealed that in primary cultures of mouse neurons, the genomic RNA of TBEV was specifically transported from the cell body to dendrites. These viral RNAs were then replicated, causing disturbance of the normal neuronal activities.

The same team recently published a study in the Proceedings of the National Academy of Sciences, where the researchers examined the transportation mechanism of the viral RNAs to dendrites. Within their study, the team identified that a cis-acting element was found to be pivotal in interacting with the transportation system. When this was mutated in TBEV, this caused a reduction in neurological symptoms in infected mice.

By studying the colocolization of viral protein and RNA with human ribosome binding proteins within neuronal granules, researchers also found that: “TBEV genomic RNA bound an RNA-binding protein of neuronal granules and disturbed the transport of dendritic mRNAs,” which is important for neurogenesis and the plasticity of synaptic communications.

Altogether, these findings have revealed that genomic RNA transport of TBEV is involved in the development of neurological symptoms following TBEV infection, and that TBEV genomic RNA interacted with neuronal granules via RNA-binding proteins and disrupted mRNA transport in dendrites.

Kentaro Yoshii (Hokkaido University), 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.”

Researchers were also able to conclude within their study that new treatment options could be developed “with virus-based vectors that can transport and express target genes locally in dendrites.”

Sources: Hirano M, Muto M, Sakai M et al. Dendritic transport of tick-borne flavivirus RNA by neuronal granules affects development of neurological disease. PNAS doi:10.1073/pnas.1704454114 (2017) (Epub ahead of print);


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