The story began in 1992, when La Scola and Raoult studied amoebas contaminating the water of a cooling tower in Bradford, England. The amoebas were infected by a microbe, which was so large that the researchers initially assumed it was a bacterium. Only later, in 2003, did they realize it was a virus—a huge one, around four times bigger than, say, HIV or the influenza virus. They called it mimivirus.
An entire world of giant viruses soon came to light: Mamavirus in a Parisian cooling tower, Pithovirus in 30,000-year-old Russian ice, and Megavirus and Pandoravirus in Chilean coastal waters. Most of these also infect amoebas, manufacturing new copies of themselves by setting up viral factories in their hosts. And these factories can themselves be corrupted by viruses.
In 2008, La Scola and Raoult noticed that amoebas infected by Mamavirus often carry a second smaller virus. This pipsqueak is a parasite that hijacks Mamavirus’s factories, using them to make copies of itself at the expense of its bigger cousin. When it’s around, the giant virus reproduces slowly, assembles abnormally, and produces daughters that are poorer at infecting amoebas. The team described the smaller virus as a ‘virophage’—an ‘eater of viruses’, a virus that sickens other viruses.
That first virophage was called Sputnik, after the Russian for ‘fellow traveler.’ More were then discovered, including Maverick virus from coastal waters, Organic Lake virophage from an Antarctic lake, and Sputnik 2 found in the inflamed eye of a French teenager.
The latest member of the virophage club is Zamilon, after the Arabic for “neighbor.” Raoult and La Scola found in 2014, and they noticed that it can only parasitize some branches of the Mimivirus family tree. Of the three such branches, one—lineage A—is immune to Zamilon.
Raoult suggested that these giant viruses defend themselves from Zamilon with some kind of CRISPR-like immune system. In other words, they contain stolen copies of Zamilon’s DNA, and using these pilfered sequences, they deploy DNA-slicing enzymes to disable the virophages. “Bernard disagreed, so we competed among ourselves to find the answer,” says Raoult, laughing.
He made three predictions. First, the A-group mimiviruses should contain DNA that matched the Zamilon virophages (which they resist), but not the Sputnik ones (which they don’t). Second, these immunizing sequences would be absent in the other two Mimivirus lineages that were not resistant to Zamilon. Third, the stolen Zamilon sequences would be accompanied by enzymes for unwinding and cutting DNA. All three predictions were true. “The war between giant viruses and virophages is similar to that between bacteria and viruses,” says Raoult.
The giant virus’s defense system, which the team calls MIMIVRE, isn’t exactly the same as CRISPR, but it is very close in form. It’s a wonderful example of convergent evolution, where two groups of living things independently come up with the same solutions to the same problems.