In a current examine, researchers from Uppsala College present that the Semliki Forest virus enters the central nervous system by first coming into the cerebrospinal fluid after which binding to a selected cell kind earlier than penetrating deeper into the mind. This discovering might probably be used to develop the Semliki Forest virus as an agent for treating mind most cancers. The examine has been printed within the journal Nature Communications.
Semliki Forest virus was initially remoted from mosquitoes within the Semliki Forest, Uganda, therefore the identify. Upon systemic an infection from mosquito bites, Semliki Forest virus causes delicate blood viremia earlier than discovering its method to the central nervous system the place it will probably trigger neurotoxicity.
It has been a longstanding quest in virology to find how the Semliki Forest virus enters the mind nevertheless it has been urged to happen by way of the blood-brain barrier. A couple of years in the past, a receptor referred to as the Very Low-Density Lipoprotein Receptor (VLDLR) was recognized as the first receptor for Semliki Forest virus when coming into host cells.
Reaches the mind in the identical manner as different viruses
Within the present examine, the Uppsala researchers verified VLDLR as the first cell entry receptor. However since VLDLR isn’t expressed by blood vessel cells within the blood-brain barrier, they reasoned that there should by one other manner for Semliki Forest virus to enter the central nervous system. They confirmed this by figuring out choroid plexus cells, the cell kind that secretes cerebrospinal fluid into the ventricles of the mind, because the gateway for neuro-invasion.
“The passage of Semliki Forest virus by way of the epithelial cell layer of the choroid plexus is strictly depending on VLDLR. This route of neuro-invasion has been demonstrated for different viruses, reminiscent of ZIKA and SARS-CoV-2, however our examine is the primary to display that Semliki Forest virus also can use this path to enter the central nervous system,” says Miika Martikainen, researcher at Uppsala College, who’s first and corresponding writer of the publication.
Might be used to deal with mind tumors
Oncolytic viruses are used as an immunotherapy in opposition to most cancers, the place the virus each invades and kills most cancers cells, and prompts the immune system to assault the tumour. Since Semliki Forest virus penetrates into the mind it’s an attention-grabbing candidate to be developed as an oncolytic agent for the remedy of mind cancers.
I’ve been engaged on Semliki Forest virus for a few years and I am more than happy that now we have been in a position to remedy this query. We are going to now focus our work on creating Semliki Forest virus as a therapeutic most cancers agent.”
Miika Martikainen, researcher, Uppsala College
When the researchers examined how effectively totally different viruses activated the immune system, the Semliki Forest virus was by far the very best. Nevertheless, it has by no means earlier than been clinically examined within the remedy of most cancers.
“The brand new information gained from our examine might have direct implications for a way Semliki Forest virus might be delivered to sufferers with the extreme mind tumour glioblastoma in a medical trial,” says Magnus Essand, researcher at Uppsala College and senior writer of the paper.
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Journal reference:
Martikainen, M., et al. (2024). VLDLR mediates Semliki Forest virus neuroinvasion by way of the blood-cerebrospinal fluid barrier. Nature Communications. doi.org/10.1038/s41467-024-55493-3.
