Researchers from Uppsala University have recently discovered that the Semliki Forest virus enters the central nervous system by first infiltrating the cerebrospinal fluid, then attaching to a specific type of cell before moving deeper into the brain. This groundbreaking finding may pave the way for using the Semliki Forest virus as a potential treatment for brain cancer. Details of the study were published in the journal Nature Communications.
The Semliki Forest virus was initially isolated from mosquitoes in Uganda’s Semliki Forest, which is how it got its name. When a person gets infected through mosquito bites, the virus causes a mild presence in the bloodstream before it travels to the central nervous system, where it can lead to neurotoxicity.
Virologists have long sought to understand the mechanism behind how the Semliki Forest virus crosses into the brain, previously suggesting that it does so via the blood-brain barrier. A few years back, researchers identified the Very Low-Density Lipoprotein Receptor (VLDLR) as the main receptor that the virus uses to enter host cells.
Similar Entry Method as Other Viruses
In this new study, the researchers from Uppsala confirmed that VLDLR serves as the principal receptor for cell entry. However, since this receptor is not found on the blood vessel cells comprising the blood-brain barrier, they concluded that there must be another pathway by which the Semliki Forest virus enters the central nervous system. They identified choroid plexus cells—known for producing cerebrospinal fluid and located in the brain’s ventricles—as the portal for the virus to invade the nervous system.
“The Semliki Forest virus’s passage through the epithelial layer of the choroid plexus relies solely on VLDLR. This route of neuro-invasion has been demonstrated for other viruses like ZIKA and SARS-CoV-2, and our research is the first to show that the Semliki Forest virus can also use this pathway to enter the central nervous system,” explains Miika Martikainen, a researcher at Uppsala University and the primary author of the publication.
Potential for Treating Brain Tumors
Oncolytic viruses are being explored as a form of immunotherapy for cancer, where the virus can invade and destroy cancer cells while also stimulating the immune system to fight the tumor. Given that the Semliki Forest virus can penetrate the brain, it presents an intriguing candidate for development as an oncolytic agent for brain cancer treatments.
“I have devoted many years to researching Semliki Forest virus, and I’m thrilled we have finally addressed this question. Our next steps will focus on further developing this virus as a therapeutic agent for cancer,” states Martikainen.
During their investigation of how different viruses activated the immune response, the Semliki Forest virus demonstrated the highest efficacy. However, it has yet to be clinically tested for cancer treatment.
“The insights gained from our study may have immediate applications for delivering the Semliki Forest virus to patients suffering from the aggressive brain tumor glioblastoma in future clinical trials,” comments Magnus Essand, a researcher at Uppsala University and the senior author of the study.
