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“Giant Virus” Found to Have Gene Editing Defense System Like CRISPR

This virus works much like the CRISPR system, and could lead to a new gene editing tool.

Joi MatthewMarch 2nd 2016
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French researchers from Aix-Marseille University discovered that gigantic mimiviruses have a defense system that is similar to the famed gene editing tool, CRISPR.

Their findings were published in Nature..

First found infecting amoeba in a water tower, this virus has a genome that us larger than most bacteria. Also, they are distantly related to viruses associated with smallpox, but they also have genes that make amino acids, DNA letters, and complex proteins.

That means that they blur the line between non-living viruses and living microbes, says Didier Raoult, a microbiologist at Aix-Marseille University, who co-led the study with microbiologist colleague Bernard La Scola.

In 2008, Raoult, La Scola and their colleagues reported that mimiviruses are plagued by viruses called virophages, just like prokaryotes. After six years, they found Zamilon, which is a virophage that infects some kinds of mimivirus, but not all. The team made a hypothesis that these infections could lead to the evolution of a defense system similar to CRISPR.

Defense System

The CRISPR system stores a library of short DNA sequences that match those of phages and other invading DNA, inside bacteria and in archaea which is a type of prokaryote. When the foreign DNA attacks a cell, specialized enzymes called “CAS” chop up the intruding DNA into pieces, which prevents infection. CRISPR has now been redesigned to be a technology that edits genomes through a similar chopping process.

Raoult’s team analyzed the genomes of 60 mimivirus strains, and tried to find sequences that would match those of Zamilon virophage. They discovered that the mimiviruses that resisted Zamilon also contained a short stretch of DNA that matched the phage.

They also found that the genes encoding enzymes can degrade and unwind DNA. In CRISPR, the genes encoding the Cas enzymes are also located beside sequences that recognize the virus. What defends them from attack is the blocking activity of different components of the system.

It makes sense for mimiviruses to have an immune system because they must compete for resources against other microbes and viruses, says Raoult. “They are facing the same kind of challenge that prokaryotes have when they live in communities: they need to fight against viruses and prokaryotes. I even suspect they secrete antibiotic compounds.”

Raoult has argued, somewhat controversially, that mimiviruses constitute a fourth domain of life — alongside bacteria, archaea and eukaryotes. He sees their defense system, which he has named MIMIVIRE, as a very ancient adaptation that further supports them having their own branch on the tree of life.

Other scientists weigh in

A microbiologist from the University of Alicante in Spain, Francisco Mójica, identified CRISPR sequences in prokaryotes back in the 1990s. He notes the the CRISPR components do exist in viruses, but it is not clear whether their systems function. He suspects that an ancestor of mimiviruses picked up MIMIVIRE from another microbe. “It will certainly be of great interest to identify the mechanism involved in MIMIVIRE immunity,” says Mójica; he expects that it will be very different from CRISPR.

On the other side of the world, a bacteriologist at the Rockefeller University in New York, Luciano Marraffini, said that Raoult’s team made a good case that MIMIVIRE is a viral defense system. He agrees that it is important to know how it stops virophage infections. Marraffini says. “The giant viruses most likely enclose a whole lot of new biology, some of which, including the MIMIVIRE, could find novel application. Maybe in genome editing, maybe in other fields.”

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