Friday, 17 February 2012

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

For those of you who read and remember my last blog post you will be familiar with the gigantic mimivirus. Mimivirus was discovered as a virus and not a bacterium back in 2003 by a team who subsequently went on to find a very closely related virus which they termed mamavirus owing to the fact that it is slightly larger than mimi. Once again the sheer size of this virus was somewhat astounding and more importantly the fact that a second giant was found makes it seem more likely that there may be more. But what was really interesting about mamavirus is that when it was first isolated it was done so with another virus in tow.

Sputnik inside mamavirus - from origional Nature paper on Sputnik

Mamavirus is roughly the same size as mimivirus, around 750nm in diameter as I described in the previous blog. However, a virus of much more classical size at 50nm was also seen under the electron microscope. This virus was named Sputnik in honour of the first man-made satellite as it was seen to be a satellite to the much larger mamavirus. Satellite viruses are not a new phenomenon, others have been observed, and at first Sputnik was thought to simply behave like the other satellite viruses in that it would infect its host (in this case an amoeba) at the same time as the larger virus and replicate itself in the host with help from the other virus. However, this was shown not to be the case - Sputnik actually infects mamavirus!

 When mamavirus infects its amoeba host it sets up “viral factories” in the cell where it can replicate its genetic material and make many new copies of itself; the term factory is highly fitting for this process as hundreds upon thousands of new viruses are turned out from these factories, allowing spread of the virus. After it was observed that Sputnik could only grow in the amoeba when mamavirus was simultaneously present, it was seen that the smaller virus actually hijacks these viral factories and uses them for its own replication, to the detriment of mamavirus. Mamavirus as a result becomes unable to replicate itself efficiently and, for want of a better term, becomes sick. Owing to its parasitic actions on mamavirus, Sputnik was coined a virophage (or virus eater).

Before Sputnik, no virus had ever been seen to directly cause damage to another virus, yet a virus infecting a bacterium is not a new idea and was first observed as early as 1915 and 1917, in independent works. These viruses that infect bacteria are known as bacteriophage, hence the logic behind the naming of virophage. I bring bacteria into the story, as one of the exciting aspects of mimi and mama is that they have begun to blur the lines between living organisms and the viruses (again refer back to the previous post). The discovery of smaller viruses that can infect these large viruses further emphasises the idea that they may be on the very cusp of being classed as alive.

Now for something exciting regarding virophage on a somewhat more practical level. I’m sure most people are well aware of the current problem we face with regard to bacterial infections. Back in 1928 when Alexander Fleming somewhat fortuitously discovered penicillin, he launched what has become commonly known as our arms race with bacteria. We are constantly producing antibiotics to limit the burden of infection from bacteria. Yet the bacteria don’t just sit back and let us kill them; they themselves are constantly looking to survive and grow, and as a result they develop protection against our interventions. We develop new antibiotics, the bacteria develop new protections and so on. This evolutionary back and forth can often lead to a steady state where neither has the advantage over the other, which has been termed the Red Queen hypothesis, after the Red Queen in Alice in Wonderland (“It takes all the running you can do to stay in one place…”). However at the present time bacteria seem to have a slight edge over us in this arms race with strains such as MRSA and multidrug resistant tuberculosis becoming ever more common, and the development of new antibiotics slowing down. As a result there is much work being done in the field to find novel prevention strategies against bacterial infection. One area that is being looked into is the potential use of bacteriophage viruses to kill the bacteria. The key to any drug is specificity as this is what makes it safe and limits the side effects, so a virus which only infects bacteria is a promising area to be looking into for ways to target bacterial infection.

Now to move away from bacteria and back to viruses. If bacteriophage can someday be used as an intervention against bacterial infection, then what is to stop us going one step further and using virophage to stop viral infection? What is to stop us from potentially producing a virophage capable of infecting HIV or influenza or any other virus you care to think of? Being that virophage are still a fairly new concept with only three known of (Sputnik, Mavirus and Organic Lake virus) the prospect of producing one capable of targeting specific viruses is some way off yet and to my knowledge not something that is being actively looked at, the current work being merely of the search for new virophage and understanding how they work. However every big idea needs the ground work of discovery and understanding in order to allow manipulation to our own ends. So perhaps in the future, instead of going to the doctors to get a drug prescription, you may head off to the doctors to get a virus. A crazy thought and something that may not be possible but nonetheless fun to think about. Much of science often starts with seemingly crazy thoughts…

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