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

Risk of congenital heart disease is determined by the age of the mother, not her eggs

As a woman of child-bearing age, I am acutely aware that the longer I postpone having children, the greater the risk that my future offspring may have a medical or developmental disorder. It seems like every few weeks, a new study makes it into the news cycle linking advanced maternal age to disease X or condition Y. (Men don’t get off scotch free – recent studies have linked advanced paternal age to autism.) A study published in Nature this week has shed light on maternal age-associated risk of congenital heart disease and risk-modifying factors.

Despite advances in diagnoses and treatment, congenital heart disease remains one of the leading causes of childhood illness and mortality. Roughly one in 100 children will have minor congenital heart disease whereas one in 1000 will require heart surgery. The risk factors for congenital heart disease include genetics, infections, maternal diabetes and advanced maternal age. A team of researchers led by Dr. Patrick Jay at Washington University School of Medicine asked whether the maternal age effect was based on the age of the mother’s eggs or the mother herself.

To tease apart these scenarios, the researchers carried out reciprocal ovarian transplants where the ovaries of young mice were transplanted into older mice and vice versa. Young mice were less than 100 days old whereas old mice were on average 318 days old (lab mice live on average two and a half years or roughly 850 days). They compared what proportion of the offspring of these two groups of mice had congenital heart disease by looking for ventricular septal defects (VSD). Ventricular septal defects are a common birth defect of the heart where there is a hole in the wall separating the lower chambers of the heart. The offspring of older mothers with young ovaries developed VSD significantly more frequently than the offspring of young mothers with old ovaries. This result provides compelling evidence that the risk of congenital heart disease is associated with the increased age of the mother and not of her eggs. Continue reading