Up until recently, viruses seemed to be simple things. Too tiny to be seen except with an electron microscope, they had compact, efficient genomes that omitted just about any gene that could be supplied by their host cells. That view started to change with the discovery of giant viruses with genomes over a million base-pairs long. These viruses carry over a thousand genes, many of which would be present in their hosts' genomes, and they can even be victims of smaller viruses.

But all of these giant viruses seemed to be related, and the viruses had a common life cycle once they infected the organisms that they preyed upon, so it was possible to view the Megaviruses as an oddball exception.

With a publication in today's issue of Science, it appears to be time to leave that comforting thought behind. In the paper, the authors describe a virus with a genome roughly twice the size of the biggest Megavirus and a viral particle that's so big it's visible with a standard light microscope. The new virus appears completely unrelated to the Megaviruses, getting its own branch on the family tree. And it has a completely different life cycle than the Megaviruses, taking over its host cell's nucleus in order to replicate.

The work was performed by a French group that has a history of studying big viruses. To get a better sense of their diversity, the group started culturing amoebas obtained from a variety of locations around the globe. They grew them in the presence of antibiotics to kill bacterial parasites and looked for cultures where the cells had a tendency to spontaneously burst (a common method of viral spread). They came up with two cultures, one from the ocean near Chile, a second from a freshwater lake near Melbourne, Australia. Later work would show that the two viruses were closely related, with the smaller of them being a compact form lacking four regions of the viral genome. We'll focus on the larger one from here on.

The first thing that was apparent was that the virus was huge. After an infected cell exploded, it left behind a lawn of particles that were roughly a micrometer long, big enough to be seen with a light microscope. Electron microscopy showed that the viruses built a thick, oval shell with a pore at one end. When an amoeba engulfed a virus, membranes in the pore would fuse with the cell's membrane, spilling the virus' contents into the cell. From there on out, the virus itself was invisible.

But there were clear signs that the virus was still active. Four hours after infection, the cell's nucleus (where its DNA is stored) started to become disorganized and fragment, later vanishing. By 10 hours, new particles started to appear, with growth starting at the pore-end and gradually building out to create a full viral particle. Eventually, each cell would burst, releasing about 100 viruses in the process.

This is nothing like the activities of the Megaviruses, which create areas that act like virus factories inside the cell, but stay away from the cell's DNA. As a result, the authors concluded this was a new group of viruses, naming them the Pandoraviruses (technically Pandoraviridae). To find out more about the Pandoravirus, the authors sequenced their genomes.

The first thing that was notable was that the genomes were enormous. The larger of the two was 2.8 million bases long, which is larger than the genomes of many parasitic bacteria (for comparison, E. coli's genome is 4.6 million bases). There were over 2,500 potential genes in that sequence, and the startling thing was how many of them were new to biologists. Only 15 percent of them lined up to known sequences, and half of those just had a small structural similarity in the middle of a larger gene. Eliminating those meant that just seven percent of the genes matched anything in our databases. Only 17 genes matched sequences found in Megaviruses, and under five percent looked like they were stolen from the host amoeba. The virus was clearly something entirely new.

Although it's hard to say much about the genes that were present (since they're completely unfamiliar), a number of things were clearly not present: nothing that could contribute to the ribosome, which manufactures proteins; key parts of the DNA copying machinery; genes for components of the pathway that extracts energy from sugars and other carbon compounds; and some of the genes needed to copy DNA. In addition, a number of the virus' genes had small sequences called introns that needed to be spliced out. None of the enzymes that manage splicing were present either. These last two things indicate that the virus has to take over the cell's nucleus, or it couldn't turn its genes into proteins or copy its DNA.

Lining up the viruses' genes with those of other families of viruses indicate that the Pandoraviruses are a distinct branch in the viral family tree, and their closest relatives are not the Megaviruses. Somehow, these viruses have escaped the DNA sequencing of environmental samples that has become very common in recent years. That said, they weren't entirely unknown to science. A dozen years ago, a lab noticed similar particles growing inside an amoeba. They simply didn't realize anything that big might be a virus.

Science, 2013. DOI: 10.1126/science.1239181 (About DOIs).