Wednesday, 8 February 2012

The biggest virus you've never heard of (post 1 of 2)

Biology loves to categorise and classify and to that end life on our planet neatly falls into 3 distinct groups: Eukaryotes (us and all life we see around us), bacteria and archaea. However, somewhere between these 3 domains of life and everything else on the planet classed as non-living sit viruses. Ask any scientist if a virus is living or non-living and you will likely get a lot of umming and ahhing and nowhere near a simple answer. The wonderful thing about viruses is that they can only be described within a certain context. When floating around in the environment, viruses are completely inert, no different from a piece of dirt or dust. There is nothing to indicate that they are alive; no growth, no energy consumption, and no chemical activity whatsoever. However as soon as a virus reaches a specific living cell it bursts into ‘life’, becoming highly active and taking over the machinery of the cell to multiply itself many times over. The general definition of a virus is as an obligate intracellular parasite, meaning it needs to be inside a cell to function and will, as a result of this, cause damage to its host. Viruses aren’t the sort of people you’d want at a dinner party as they’d eat all the food you cook, all the food in the kitchen and then trash the house just for good measure, before smashing the windows to leave instead of using the door. While viruses have long been thought of as an entity unto themselves who lurk over all 3 domains of life like a heavy rain cloud, this view is starting to shift. In this blog I’d like to discuss a couple of viruses that are completely changing the classical view of viruses and blurring the boundaries between viruses and the other domains of life.

Back in 1992 an outbreak of pneumonia hit Bradford (UK) and the investigation into the causes led researchers to discover what they thought was a new strain of the Legionella bacteria which they isolated from an amoeba found in a cooling tower. To the team who made this discovery it seemed perfectly reasonable to assume that what they had discovered was a bacterium; it was huge and took up a classic marker stain for bacteria known as the Gram stain. However over a decade later a new team looked at this supposed bacterium and using new high powered microscopes discovered that it was in fact a virus, which they termed “mimivirus” in honour of its ability to mimic a bacterium. The first team weren’t stupid, this virus looks nothing like any other virus known of at the time; for one, it is huge (comparatively). To give some sense of scale: a pin head is usually around 2mm in diameter, a typical red blood cell has a diameter of about 8 micrometres (that’s 0.008mm) and a typical bacterium is about 1 micrometre (0.001mm or 2000 times smaller than a pin head). Getting even smaller, the typical virus is a mere 75 nanometres (that’s a miniscule 0.000075mm). So an average bacterium is around 1000 nanometres and a typical virus is about 75 nanometres;mimivirus is in the region of 600-750 nanometres, a giant amongst viruses and even bigger than a number of bacteria. Hopefully I haven’t lost you with all the numbers but the bottom line is that mimivirus is around 10 times larger than other viruses; imagine bumping into a man who’s 51 feet tall!
EM image of mimivirus

As if the sheer size of this new virus isn’t enough, the tale of mimivirus gets even more interesting. Shortly after it was found to be a virus, people started to look at its genetic material, and what they found shocked the virology community. Viruses always need to infect a host since they are incapable of making proteins or energy (metabolism) for themselves, as they lack any genes that allow them to achieve this. The abilities of metabolism and protein synthesis are thought of as hallmarks of life and are part of the argument against viruses being alive. The thing about mimivirus is that it has many genes needed for both of these processes, meaning that mimivirus is nearly capable of ‘living’ independently of a host. This is a tantalising prospect, as having the ability to replicate and consume energy independently is something only living organisms can do, so the lines between the 3 domains of life and viruses are beginning to blur.

But what does this mean? It is proposed by some that mimivirus may have had an evolutionary ancestor that was even more independent that it is now, potentially to the extent of not needing a host and therefore not being a virus by our definition. It is claimed that over time this virus became more dependent on a host and lost some of its abilities, leaving us with the virus we see today. However nothing in science is straight forward and some argue against this ‘regression model’ of evolution and instead assert that mimivirus has acquired these complex genes from other organisms, some stolen from the amoeba they infect and others from bacteria that can simultaneously infect the amoeba. 

I don’t intend to pick sides in the debate over the origin of the genes, however let us pretend that the argument for regression evolution turns out to be the case, as this would have some very big implications that are fun to think about. Some of the genes mimi has are seen to be conserved among viruses that infect all 3 domains of life. When a relationship like this is seen in evolution it usually means that somewhere in the distant past there was a shared ancestor. To use Darwin’s brilliant tree of life metaphor for evolution, it is possible that a close ancestor of mimi may be the one which sat at the very base of the virus tree and therefore gave rise to all other viruses. This argument isn’t perfect since the question can be raised as to why mimivirus has stayed so close to the ancestral virus when other viruses have moved away so much, but an exciting idea nonetheless.
Darwin's sketch of the tree of life

However, some go even further and argue that the mimi ancestor may also have been the seed that started the Eukaryotic tree to which we belong. I have previously written a blog regarding the evolution of Eukaryotic cells, but that blog was looking at the endosymbitoic theory and the ability of cells to produce energy, it did not look at the nucleus. The nucleus is often referred to as the brain or the control centre of the cell as it houses the DNA which has the potential to control the cell. The nucleus is what separates complex, Eukaryotic life from the simple bacterial and archael life and its origin is a contentious issue. It is proposed by some that a mimi-like virus may be the origin of the nucleus. Like us mimivirus has a DNA genome so it is possible that a mimivirus ancestor could have entered a simple cell and instead of damaging and destroying it, could have instead set up residence in its host and entered a symbiotic relationship instead of a pathogenic one, given the birth of nucleated life which, billions of years later, would give us the world we see around us.

Who would have thought back in 1992 that an outbreak of pneumonia in Bradford would lead to the discovery of a virus with the potential not only to change many fundamental concepts of virology but also to shine a light on the birth of complex life? As if that isn’t enough, a very similar virus to mimivirus was also discovered termed mamavirus which has given rise to a completely novel concept of viruses, the virophage which I will discuss in my next blog. So come back soon.

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