Up until recently, the line between viruses and cells seemed pretty simple: cells were big and carried everything they needed to live and grow. Viruses were tiny and only carried the genes they needed to take over their host cells; they relied on their hosts for most essential proteins.

That line got a bit blurry as we found parasitic and symbiotic cells with very stripped-down, minimalist genomes that wouldn't let them survive outside their hosts. But it's nearly been obliterated by the discovery of giant viruses—some of these have genomes that are larger than those of bacteria and carry many of the genes needed to copy DNA and translate it into proteins.

Scientists have now identified yet another giant virus, this time using a technique that sounds like it's straight out of a sci-fi horror flick: they thawed some 30,000-year-old permafrost and allowed any viruses present to infect some cells. Fortunately, the cells were amoebas, and this virus is overwhelmingly unlikely to present a threat to human health. But the fact that viruses could apparently survive so many centuries in the Siberian permafrost does lead the authors to suggest that the melting Arctic may pose an emerging disease risk.

The authors of the new paper, a mix of French and Russian researchers, identified the virus using a procedure that's incredibly simple: take a culture of amoebas (a strain that has been found in the permafrost) and put a bit of permafrost in with the culture. After that, it was a matter of waiting for something bad to happen to the amoebas.

The something bad in this case happened to be the explosion, or lysis, of the cells. A check of the culture showed the presence of a giant virus particle, shaped similarly to the Pandoravirus described in the article linked above. In terms of the sheer physical size of the virus, it's the largest one we've yet discovered. Because of its jug-like shape, the authors named it Pithovirus after a type of amphora used by Pandora (the namesake of the second largest virus).

However, there were some clear differences with Pandoravirus from the start. For example, the cork of the jug (their term, not mine) appears to contain some specialized fibers that are unlike anything seen in Pandoravirus. And the Pithovirus reproduces in a virus factory it sets up inside infected cells; the Pandoravirus takes over a cell's nucleus. (Viral factories are also set up by the first giant virus identified, Mimivirus, which looks physically distinct from these other two.)

Despite its giant physical size, Pithovirus carries a relatively small genome at only 600,000 DNA bases long. Some of the extra space inside the virus is taken up by the proteins needed to get the virus' replication started after infection (RNA transcription machinery). But the authors are at a bit of a loss to explain what all the extra space inside the virus' capsule might be used for.

The genome is also small in another sense: gene content. It encodes only 467 proteins, far fewer than the 1,000 to 2,500 genes carried by other giant viruses. Missing are the sorts of things that make the other giants unique among viruses: genes for translating RNA into proteins and others involved in energy metabolism. Also unusual is the presence of repetitive DNA. Viruses normally get rid of any unused DNA sequences, leaving most of their DNA taken up by protein-coding genes. Pithovirus has a large collection of nearly identical, non-protein coding sequences.

The authors suggest two options: either that the virus just needs the extra DNA as padding to make it large enough to work in its giant shell, or it has recently been invaded by some parasitic DNA and hasn't had the chance to get rid of it via evolution. (Although they can't rule out other possibilities right now.)

As far as the genes themselves, only a third are similar to anything we've ever seen before. And that third is divided roughly equally among similarities to genes from bacteria, the virus' eukaryotic host, and other viruses. All of which means that Pithovirus is a distinct type of virus from anything we've ever seen before. It does seem to be distantly related to some other viruses we've previously identified, but those aren't giants like this one.

So far, all of the giant viruses we've identified infect amoebas, and the authors chose to go this route when searching permafrost explicitly because it seemed safe. Anything that came out of the search was very unlikely to infect humans. But they consider the search itself a proof-of-principle: they took care not to contaminate the permafrost, which was still frozen when it was obtained. That means that the virus is very likely to have survived 32,000 years of deep freeze, which is how old the layer it came from appears to be.

All of which, the authors suggest, should be a warning. There are already humans living in areas with permafrost, and many more are expected to arrive there as the thawing Arctic makes exploitation of natural resources there much easier. The new find suggests that some of the new arrivals may potentially come in contact with infectious agents that have been out of circulation for tens of thousands of years. This doesn't mean the permafrost will necessarily be a hotbed of emerging diseases, but the authors argue that we might want to take the possibility seriously.

PNAS, 2014. DOI: 10.1073/pnas.1320670111 (About DOIs).