Zoologger: The only virus with an immune system

Zoologger is our weekly column highlighting extraordinary animals ? and occasionally other organisms ? from around the world

Species: the ICP1 bacteriophage ? and its victim Vibrio cholerae
Habitat: identified in south Asia, engaged in mortal battle

The tiny virus, barely 200 nanometres long, is about to infect its favourite victim: Vibrio cholerae, the species that causes cholera. This vast bacterium has an arsenal of defences that help it get rid of viruses, but they will be no good this time.

That's because the attacker, ICP1, has a secret weapon. It carries a set of immune system genes that one of its ancestors stole from a previous victim. Immune genes are normally a form of self-defence, but ICP1 uses them as assault weapons. With these big guns, it overpowers the bacterium's defences.

Healthy bacteria

Most living things have an innate immune system: a set of mechanisms that fight off potential infections. Humans, for instance, have cells called phagocytes that eat invading bacteria, and bacteria have special enzymes that latch onto viral DNA and cut it to pieces.

But some organisms also have an adaptive immune system, which "remembers" diseases it has been exposed to, so the next time it meets them it can handle them better. This is the basis for vaccination, which uses weakened versions of a disease to prime us for the real thing. Until 2007, it was thought that only vertebrates had an adaptive immune system.

In fact, many single-celled organisms have one. Bacteria often carry repetitive genetic sequences called CRISPRs, which protect them against viruses.

When a bacterium is attacked by a virus, it copies a small piece of the virus's DNA and stores it among the CRISPRs. The bacterium will then be better at fighting off the virus: the bacterium can acquire resistance, just like a human acquiring resistance to a disease.

The CRISPRs are a library of diseases, storing samples of past infections. If the same kind of virus attacks again, the bacterium is ready. Any viral genes that enter the cell are quickly marked for destruction.

To do this, the bacterium makes copies of the viral DNA samples. These float inside the cell and latch onto any virus genes they find. A family of proteins known as Cas proteins are then attracted to the scene, and cut the virus genes to pieces.

The bacterium can store new memories by incorporating new fragments of DNA every time it is attacked, says John van der Oost of Wageningen University in the Netherlands. "It's an immune system and it's adaptive." The system is found in 40 per cent of bacteria and 90 per cent of archaea, which means the adaptive immune systems of vertebrates are far from unique.

Turning the tables

But the war isn't over. Viruses are notoriously adaptable. According to Andrew Camilli of Tufts University in Boston and colleagues, ICP1 has managed to turn the CRISPR system to its own advantage.

Camilli discovered ICP1 in 2011, and found it to be common in cholera bacteria in Bangladesh. The surprise came when his team found ICP1 had its own CRISPRs, and genes for the Cas proteins, probably stolen from a bacterium.

Camilli looked at the genetic samples stored in the virus's CRISPRs, and found that two of them were identical to a section of the V. cholerae genome. Better still, these bits of DNA are involved in other aspects of the bacterium's immune response.

The implication is that at some point, the virus must have stolen part of the bacterium's arsenal and re-programmed it to target what was left.

When Camilli and his colleagues mutated the virus's CRISPR DNA, the virus lost its ability to infect the bacterium. Further experiments suggested that the virus uses the CRISPRs in the same way that the bacterium does: labelling the relevant bits of bacterial genome, and then destroying them with Cas proteins.

It's yet another twist in the long-running battle between bacteria and viruses, says van der Oost. "You have every kind of warfare you can think of in the microbial world. That is why it evolves so fast."

"You could maybe exploit this feature to attack nasty bacteria," he adds. In theory, a virus could be engineered to attack a dangerous species of bacteria, by giving it CRISPR sequences and the correct samples of bacterial DNA. "You could give it even more power."

Journal reference: Nature, DOI: 10.1038/nature11927

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