Viruses are skillful mutants, changing their structures or outer proteins to evade the shifting natural defences of their targets. That’s why you have to get a flu shot every year, and endure the seasonal week-long bout of the common cold (typically the fault of rhinoviruses). But scientists in France are looking at viruses in a significantly different light - they’re harnessing the power of one of viruses’ most proficient mutators, HIV, and using it to fight another intractable disease: Cancer.
A team of scientists at the French National Center for Scientific Research set out to study molecules that could improve the effectiveness of cancer drugs. This process often involves screening for desired traits using bacteria, but sometimes, a molecule that works one way in a bacterium will work totally differently in a human cell. The team realised that it would be far more efficient to both find new compounds and screen for them inside human cells - and to speed up the “finding” part of the process, they worked with HIV, taking advantage of both its replication machinery and high mutation rate.
As HIV replicates, it creates slightly new versions of itself over successive generations. This allows it to resist most of the drug cocktails and anti-viral treatments developed to fight it, but also makes it a powerful molecular tool: A mini factory that churns out new, subtly different compounds that work in slightly different ways. The CRNS team was interested in developing a more potent form of deoxycytidine kinase (dCK), a protein found in all cells that’s crucial for activating most anti-cancer drugs. The scientists hypothesised that if they could make a more potent form of dCK, the cancer drugs we have would work more effectively - causing lower required doses, minimised side effects, and less toxicity exposure for healthy cells.
“Mutant HIV”, complete with different takes on the dCK protein, were replicated through several generations, yielding an entire library; about 80 different mutants of dCK were isolated in total. Ultimately, they located a variant that induces tumour cells to die with just 1/300th the dose of cancer-killing drugs. There’s no doubt about it; this one-two protein punch is an effective tumour killer.
The discovery is notable for a few reasons - first, the mutated protein was shown to work in human cells; this is a massive deal, as a lot of the research we see published in the science sections of newspapers has had glowing success in animal trials, but hasn’t been tested in human cells yet. Second, it suggests weakening the tumour’s resistance to anti-cancer drugs could be instrumental in fighting and possibly curing the disease. Finally, it suggests a novel therapeutic use for one of humanity’s deadliest viruses - awesome.
It’s worth noting, though, that this technology certainly won’t be tumour-zapping in hospitals tomorrow: it’s got many more tests to go through before it gets to that stage. The “right-now” implications of this research are HIV’s use as a molecular factory for generating slightly mutated variants - which could have applications across a whole range of scientific fields.
Image, top: HIV-infected T-lymphocyte. Image, bottom: Dividing tumour cells.
The paper was originally published in PLoS Genetics. An article was also written in ScienceDaily about the subject.