CRISPR-like immune system found in giant virus

Researchers have found that mimiviruses, a class of giant viruses, have an immune system reminiscent of the CRISPR system used by bacteria to evade infection.

As CRISPR has been adapted by scientists as a powerful genome-editing tool, the finding raises the possibility that this newly discovered system – dubbed MIMIVIRE – could be harnessed in a similar way.

Mimiviruses were first discovered by the same team of researchers 13 years ago. They are around four times the size of other viruses like HIV or influenza and can contain hundreds more genes.

A few years ago, the researchers, led by Professor Didier Raoult of Aix-Marseille University in France, found that a type of virophage (a virus that infects other viruses) could infect mimiviruses and stop them replicating. However, some types of mimivirus were resistant to virophage infection.

Professor Raoult and his team suspected this resistance might have its origins in an immune system similar to that found in bacteria. CRISPR sequences are a library of DNA from invading phages and plasmids contained within the bacterial genome that allow the micro-organisms to recognise an attack. Cas enzymes encoded in nearby genes then unwind and cut the invading DNA, putting a stop to the infection.

By analysing the genomes of virophage-resistant mimiviruses, the researchers identified at 28-letter stretch of DNA which was identical to a sequence found in the virophage. Part of this stretch was also repeated another four times, but was not found in non-resistant mimiviruses, leading the researchers to conclude that the sequences are linked to immunity against virophages.

Furthermore, adjacent to these stretches, the team found two genes encoding enzymes with the ability to unwind and slice DNA – just like in the CRISPR/Cas system. Blocking these genes made the mimiviruses vulnerable to virophage attack.

The researchers say the discovery of the MIMIVIRE system supports their assertion that mimiviruses represent a unique and ancient branch of the tree of life. But the evolutionary history of the giant viruses is still under debate.

Professor Raoult told STAT that it might be worth exploring the use of MIMIVIRE as a genome-editing tool. 'It is different, so it may have different applications,' he said.

CRISPR pioneer Professor Jennifer Doudna, from the University of California, noted that the new research didn't make exactly clear how MIMIVIRE works, but said that 'the potential for such a system to be harnessed for genetic control is intriguing'.