Friday, 7 March 2014

Pithovirus - More than just a large storage container

I have a fascination with giant viruses; they have made two previous appearances on my blog (here/here and here). The reason for this fascination is two-fold; firstly, their discovery shattered the notion of viruses as tiny, sub-microscope, particles and secondly, because they have resulted in some intriguing ideas surrounding the beginning of life itself and even the suggestion of a fourth domain of life (see the two previous posts for more details). It has been over 10 years since the first of these giant viruses, Mimivirus, was characterised. Following that discovery, multiple related viruses were identified, and the Megaviridae family was defined. It was thought that these viruses were the only family of giant viruses, one (literally) huge exception amongst a plethora of viral families. That was until the discovery of Pandoravirus, a virus that was even larger than any members of the Megaviridae, and, moreover, completely different. This opened the door for there to be more families of giant viruses, the Megaviridae were no longer an exception. A third viral family has now entered the furor, sitting somewhere between the two previously defined families - this is Pithovirus.

The name derives from the Greek pithos meaning ‘large storage container,’ and was chosen for the fact that a pithos was given to Pandora (Pandora's box) - hinting towards the link with Pandoravirus. The two viruses look very similar as you can see in the images below. Additionally, the naming, either deliberately or fortuitously, hints at another feature of Pithovirus - that being its size. It is even larger than Pandoravirus (the previous giant virus record holder) measuring 1.5 micrometers in length and 0.5 micrometers wide - making it a ‘large storage container’ indeed (as viruses go anyway). To put that size in context, influenza virus is roughly spherical, with diameter of approximately 0.1 micrometers.
Pandoravirus (false colouring for display)
Pithovirus (false colouring for display)

What's even more intriguing about the size of Pithovirus is the fact the genome is comparatively tiny. Pandoravirus measures at 1 x 0.5 micrometers, and weights in with a genome of 2.8 million base pairs of double stranded DNA (the same genetic building blocks we use). However, the physically larger Pithovirus has a genome of only 610,033 base pairs - about 4.5 times smaller than Pandoravirus. Additionally, while the two viruses may look similar from the outside, their genomes are completely different. DNA is made up of bases, of which there are 4: A, T, C and G. The genome of Pithovirus is 64% AT, whereas Pandoravirus is 61% GC. Furthermore, there are only 5 proteins made by Pithovirus that have any similarity those of Pandoravirus.

It seems strange that Pithovirus has such a large shell to encase, comparatively, such little genetic material. The virus Phaeocystis globosa has a similar sized genome, but this is encased in an icosahedron of only 0.15 micrometers in diameter.

One possible explanation for the discrepancy between the viral particle size and genome size could be due to gene loss - an idea suggesting that viruses originate from independent cellular organisms that lose genes and become dependent on a host. Perhaps Pithovirus has lost genes and become parasitic, but has not evolved into a small particle. (See the Pandoravirus blog for more details about the idea of gene loss).

An alternative explanation for the size of Pithovirus could be that this feature is essential for its lifecycle. Pithovirus is a virus that infects amoeba, and indeed, it's ability to infect Acanthamoeba castellani was how it was discovered. This is something in common between all the giant viruses - they all prey on amoeba. Amoeba are single celled organisms that obtain nutrients (eat) through a process known as phagocytosis - the same process our macrophages use to engulf foreign organisms and protect us from infection. Could it be that these viruses need to be giant to ensure that amoeba confuse them for nutrients and phagocytose them? Without being phagocytosed, the virus would not be able to enter the amoeba and could not replicate. Viruses are incredibly adept at subverting essential mechanisms of a cell to their own end, so perhaps the sheer size of these viruses is another example of this. It will be interesting to see, as more giant viruses are discovered, whether any can infect organisms that do not rely so heavily on phagocytosis. 

Not only is the size of Pithovirus fascinating, but also how it was discovered. The team, working from the labs of Jean-Michel Claverie and Chantal Abergel, obtained samples of Siberian permafrost dating back approximately 30,000 years. Using these permafrost samples the teams then inoculated cultures of Acanthamoeba castellani and found that Pithovirus was able to grow from these cultures. What is truly remarkable about this is that Pithovirus had been frozen in Siberian permafrost for over 30,000 years and could be thawed out and become infectious. This makes it the oldest infectious organism ever discovered.

The discovery of Pithovirus in 30,000-year-old permafrost does beg the question about what else might be lurking in sediments hidden away in the Siberian ice. Climate change in the Russian Arctic is more evident than many other parts of the world, having seen a 3°C temperature increase in the last 100 years, compared to a global average increase of 0. 7°C. As the ice thaws, it may be possible that other ancient infectious organisms could be released. While this study does not say that this will happen for sure, it makes it clear that surveying permafrost regions may be an important scientific expedition, not just to detect anything dangerous, but also to potentially uncover new and exciting organisms.

The discovery of Pithovirus is fascinating as it adds yet another layer of complexity to our understanding of the giant viruses. It seems to sit somewhere in between the two previously describe families, looking like Pandoravirus, but being genetically more closely related to members of the Megaviridae. It was a pithos that Pandora received from the Gods containing all the worlds’ evils. While Pithovirus is not going to bring any evils to anything other than amoeba, the fact that a virus can be preserved for that long in Siberian permafrost does come with a warning that more exploration may be important. And not only important, but also exciting, who knows what we may find!

1 comment:

  1. Giant viruses of the Pithovirus type have been isolated inside Acanthamoeba sp.-from surface water long time before its final identification as Pithovirus sibiricum.(Hoffmann et al. 1998).see for yourself: review:: Michel et al. Journal of Endocytobiosis and Cell Research (2013) 24: 12-15 (open access)