Introducing Lassa-VSV, a hybrid virus that kills brain tumours

Electron microscopy image of vesicular stomatitis virus particles (Image: Dr. Frank Fenner)
Electron microscopy image of vesicular stomatitis virus particles. The bar represents 100 mm. (Image: Dr. Frank Fenner)

Last month, I wrote about using Salmonella to deliver anti-cancer compounds to tumours. Today, I’m sharing with you a paper on cancer-fighting viruses. Why the recent focus on microbiology and cancer? Because they’re much more interconnected than you would think and because they’re both so cool! (And maybe also because I’m a microbiologist and my husband is a cancer geneticist so it’s kind of like a mash-up of us.)

By now, most people will have heard of viruses that can cause cancer, the most well known example being human papillomavirus (HPV) and cervical cancer. But did you know that some viruses can also destroy cancers? These oncolytic viruses infect cancer cells and hijack the cell’s machinery to make lots and lots of new viruses. Eventually, the cancer cell becomes so full of viral progeny that it bursts open and dies. In doing so, it releases its cargo of oncolytic viruses to infect neighbouring cancer cells. When these viruses infect normal, healthy cells, the cells use their anti-virus immunity to prevent the invaders from taking over their machinery and making new viruses. In cancer cells, these anti-virus immune systems are weakened or disabled, giving the viruses free rein over the cells’ resources.

Vesicular stomatitis virus (VSV) is particularly good at attacking tumours. In preclinical studies, VSV has been successful in targeting a number of different cancers, including cancers of the prostate, breast, liver and colon. Furthermore, VSV has shown great potential in treating brain tumours, a disease for which treatment options are limited and prognoses are typically poor. One of the major obstacles to using VSV to destroy brain tumours is safety. While VSV preferentially targets and kills tumour cells, it also attacks normal brain cells, leading to harmful effects on motor coordination, behavior and other neuronal processes.

The neurotoxic effects of VSV seem to be primarily caused by a special protein on the surface of the virus, known as a glycoprotein or G protein. In a paper published this past week in the Journal of Virology, researchers at Yale University and Harvard University tried to overcome the neurotoxicity of VSV by engineering a hybrid virus. The researchers wanted to know if swapping out the G protein of VSV with the G protein from another virus would lessen the harmful effects of VSV on the brain while maintaining its tumour-killing abilities. Continue reading