For most of my research career, I worked on viruses with small genomes, such as poliovirus and HIV. For me, the attraction of these viruses is that it is easier to understand all the interactions that go on within a small genome than with an unfeasibly large genome such as that of a cell. However, in the past few years I have become fascinated with a group of viruses that are not only considerably bigger than the little guys I worked on, but indeed the biggest of all known viruses. It has to be said that virologists are possibly not the most imaginitive people when it comes to names, so we called them all Giruses – giant viruses.
It all started in 2003 with the discovery of a new virus with a very big genome which was found hiding inside another microbe, Acanthamoeba polyphaga. This virus was so big that it had in fact first been seen ten years earlier in a Gram stain and mistakenly thought to be a small Gram-positive bacterium. Yes, these viruses are bigger than some bacteria, which finally puts paid to the persistent exam answer that size is one of the differences between bacteria and viruses. This giant virus (400 nm in diameter and with a genome of 1.18 million base pairs (bp, Mbp) of double-stranded DNA) was called Mimivirus for “mimicking microbe” – because we were dumb enough to think it was a bacterium for 10 years. (Embarrassingly, that’s not the first time this has happened. Poxviruses are just about large enough to be seen with very good light microscopes and were originally though to be bacterial spores, and in the 1903 Adelchi Negri thought that the virus factories now named after him found in rabies virus-infected cells were sub-cellular organelles.)
They’re getting bigger
As the years went by, the viruses got bigger. In 2010 we found Megavirus chilensis in a water sample collected in off the coast of Chile. At 500-600 nm diamater and with a genome of 1.25 Mbp, Megavirus just outpips Mimivirus. Then it started to get weird. Not only were these viruses bigger than some small bacteria such as Mycoplasma, we also found they had their own viruses. The Sputnik virophage replicates in amoeba cells that are already infected by a giant helper virus – Mamavirus.
There’s no reason to think this trend is going to stop just yet, and just this week the largest virus yet discovered has hit the press. Pandoraviruses are amoeba viruses with genomes of up to 2.5 Mbp, reaching the size of not only bacterial genomes but even some simple parasitic Eukaryotes. At 700 nm diamater and with well over 1,000 genes, the Pandoraviruses were named because they open a big box of trouble for people who still cling to the thought that you can classify organisms based on how big they are.
Do big viruses make you really sick?
Having a big genome isn’t really that important, it’s what you do with it that counts. And with viruses, a key question is – do they make you sick? The jury’s still out on that point. Although you can find antibodies against Mimivirus and some of it’s relatives in people with pneumonia, and Mimivirus has recently been isolated direct from patients with pneumonia, that is not definitive proof that the virus is causing the disease rather than simply being a passenger. The association of these viruses with amoebal hosts is particularly difficult in this respect. Until we have been properly able to satisfy Koch’s Postulates we won’t know for sure. And Robert Koch wasn’t working in the era of modern medical ethics, so those experiments are a lot harder to do now. Mamavirus and Pandovirus was pulled out of seawater so we have no idea if it has disease-causing potential, large or small.
So have all these giant viruses has blown my reason for liking bonsai viruses out of the water and given me virus envy? Nah, small is still beautiful in my view :-)