Researchers at Uppsala University have uncovered how the Semliki Forest virus (SFV) gains access to the central nervous system (CNS), paving the way for its potential use in treating brain cancer. Originally isolated from mosquitoes in Uganda’s Semliki Forest, SFV typically causes mild blood viremia upon systemic infection through mosquito bites. However, it can eventually reach the CNS, leading to neurotoxicity.
Key Findings
The study, published in Nature Communications, demonstrates that the virus enters the CNS by first passing into the cerebrospinal fluid (CSF) and then targeting specific cell types before infiltrating deeper into the brain. This discovery could open new avenues for developing SFV as an oncolytic agent for brain cancer therapy.
Entry Pathway into the CNS
Historically, virologists believed that SFV entered the brain via the blood-brain barrier. However, recent findings confirm the virus uses a different pathway. SFV exploits the Very Low-Density Lipoprotein Receptor (VLDLR) as its primary entry receptor, but since VLDLR is not present on blood vessel cells in the blood-brain barrier, researchers sought alternative explanations.
Their investigations identified the choroid plexus—a structure responsible for secreting CSF into the brain ventricles—as the entry point. The virus utilizes VLDLR to penetrate the epithelial cells of the choroid plexus, a mechanism shared by other viruses like ZIKA and SARS-CoV-2.
Implications for Brain Cancer Treatment
SFV’s ability to invade the CNS has inspired researchers to explore its potential as an oncolytic virus for brain cancer treatment. Oncolytic viruses work by directly killing cancer cells and activating the immune system to attack tumors.
“Our findings mark a significant step in understanding SFV’s entry pathway into the brain,” said Miika Martikainen, lead author of the study. “We are now focusing on developing SFV as a therapeutic agent for brain cancers like glioblastoma.”
When tested for its ability to stimulate immune responses, SFV outperformed other viruses, making it a promising candidate for cancer immunotherapy. Although SFV has yet to be clinically tested for cancer treatment, the new insights from this study could influence its application in future clinical trials.
Conclusion
The groundbreaking research from Uppsala University sheds light on SFV’s unique entry mechanism into the brain and highlights its potential role in treating aggressive brain tumors. By advancing our understanding of viral pathways and immunotherapy, this study paves the way for innovative cancer treatments.
For more updates on this exciting development, stay tuned to the latest research advancements in virology and cancer therapy.
References:
Miika Martikainen, Roberta Lugano, Ilkka Pietilä, Sofie Brosch, Camille Cabrolier, Aishwarya Sivaramakrishnan, Mohanraj Ramachandran, Di Yu, Anna Dimberg, Magnus Essand. VLDLR mediates Semliki Forest virus neuroinvasion through the blood-cerebrospinal fluid barrier. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-55493-3
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