Of mimiviruses and making progress

It’s been so long since I’ve written anything about CRISPR that I feel completely rusty. Luckily, I spotted some interesting new research on an “immune system” found in giant viruses called mimiviruses. Levasseur et al. (2016) propose that mimiviruses – large viruses that can be seen with a light microscope and have a genome that is bigger than that of some bacteria – can defend themselves against so-called virophages. In analogy to the viruses that infect animals, bacteria can be infected by viruses called bacteriophages, and mimiviruses can be infected by virophages. Although generally viruses are regarded as non-living these giant viruses do possess some genes that code for proteins that help build the virus. Normally, viruses hijack the infected host cell’s machinery to replicate and are completely dependent on the host cell. Only last year a group reported (Ekeberg et al., 2015) using high power X-rays to study a single virus and being able to look inside the particle. There is a nice 3D reconstruction video in the Nature News & Views article.

One of the virophages that infects some mimivirus lineages, but not others, is called Zamilon. Levasseur et al. guessed that mimiviruses  might incorporate stretches of DNA from Zamilon and use them to recognise infecting virophages. This would be in complete analogy to many bacteria and archaea that protect themselves from their attackers using CRISPR – clustered regularly interspaced short palindromic repeats. The DNA “spacers” correspond to the sequences found in the invading DNA  of bacteriophages, for example. To test their idea, Levasseur et al. sequenced the genomes of 45 mimivirus strains and did indeed find a repeating region that corresponded to Zamilon DNA. They called it MIMIVIRE, for mimivirus virophage resistance element (the figure is copied directly from the paper):

Screen Shot 2016-03-05 at 21.30.06

Schematic of the mimivirus MIMIVIRE locus – copied directly from Levasseur et al., 2016

Nearby in the mimivirus genome the researchers also found (Cas-like) genes that might be involved in this defence mechanism: when those genes were genetically silenced the viruses that were normally resistant became sensitive to Zamilon infection. Furthermore, these Cas-like genes code for proteins that can bind and modify DNA and are therefore perfect candidates for destroying invading DNA. More experiments will need to be carried out to show exactly how the MIMIVIRE system works, but it is likely to be different from the CRISPR/Cas system. However, it is interesting to see how immune systems are pervasive in all domains of life (and almost life) and although I am no evolutionary biologist I think this may be an example of convergent evolution. [Thoughts on this would be appreciated!]


To end today’s post on a personal positive note: this year’s birthday present was being able to image the cells I am studying by electron microscopy. Electron microscopes are, in principle, similar to light microscopes, which most of us have used at school, except that they utilise electron beams instead of light rays as the source of illumination. Since electron beams have a much shorter wavelength (i.e. are higher in energy) than visible light they can visualise objects with much higher resolution, making it possible to get sharp images at greater magnification. Some of the images we – the extremely knowledgeable and helpful scientists at the electron microscopy facility in our institute and I – took were magnified 60,000 times!

Although I can’t share those images at the moment, here is a transmission electron micrograph of a normal pancreatic ductal cell (copied directly from here):

wt ductal cell

Pancreatic ductal cell

In the centre of the cell is the large nucleus, clearly defined by its double membrane. The darker patches within the nucleus are parts of the DNA that are more tightly compacted than others. In the cytoplasm (the area that isn’t the nucleus) there are some mitochondria, where a lot of the cell’s metabolism takes place, and so-called endocytic vesicles, membrane-bound compartments that are involved in recycling and housekeeping. At the top left are microvilli, short protrusions of the cell into pancreatic duct. Although I’m not sure I can spot it here, the images we took also revealed the rough endoplasmic reticulum where ribosomes sit and produce proteins. Can you believe I saw ribosomes?!

Lastly, and this goes out mainly to all the other PhD students, I’ve recently been finding it helpful and refreshing to relish the feeling that, as a student, there is always so much more to learn. To really bask in the glory of one’s own ignorance and then pester and listen to more knowledgeable and more experienced people to learn something new. For example, you can plan a decent experiment that has the proper controls and would give you some useful information. Then you tell your supervisor about it and s/he suggests doing that little extra something that suddenly turns the experiment into real science. On the one hand, I find these occurrences humbling. But, on the other hand, they are also exciting because I’m finding it easier and easier to recognise what makes a really good experiment and I can see, still beyond my reach but tantalisingly close, the potential of making that last mental leap myself. Needless to say that doesn’t at all mean that an experiment will technically work…


References:

Ekeberg T, Svenda M, Abergel C, Maia FRNC, Seltzer V, Claverie J-M, Hantke M, Jönsson O, Nettelblad C, van der Schot G, Liang M, DePonte DP, Barty A, Seibert MM, Iwan B, Andersson I, Loh ND, Martin AV, Chapman H, Bostedt C et al. (2015) Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser. Physical Review Letters 114: 098102

Levasseur A, Bekliz M, Chabrière E, Pontarotti P, La Scola B, Raoult D (2016) MIMIVIRE is a defence system in mimivirus that confers resistance to virophage. Nature advance online publication

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