Megavirus, the biggest known virus

14 December 2011

megavirusThe mantle of world’s biggest virus has passed from Mimivirus to Megavirus. But in this case, size doesn’t matter. It’s the genes that these viruses share and do not share that make this story important.

The discovery of Mimivirus in a French cooling tower amazed virologists. At 750 nanometers in diameter, it dwarfed all other known viruses and shattered the notion of viruses as ‘filterable agents’. That definition came from using filters that exclude any particle larger than 200 nanometers. The 1.2 million base pair Mimivirus DNA genome was found to encode 979 proteins – more than any other virus. This treasure chest included some proteins never found in any viral genome, such as amino-acyl tRNA synthetases, the enzymes that attach amino acids to transfer RNAs in preparation for protein synthesis. Many other cellular genes were also encoded in the Mimivirus genome, as well as proteins that had never been seen before. This discovery led to the idea that Mimivirus evolved from an ancestral cellular organism by losing genes. The alternative idea is that viruses are ‘pickpockets’ – they began as small pieces of DNA that escaped from cells, acquired a capsid, and then slowly stole genes from other organisms.

The problem with the idea that Mimivirus is a gene loser is that it was the only really big virus of its kind – until Megavirus was discovered in the ocean off the coast of Chile. At 680 nm in diameter, Megavirus is slightly smaller than Mimivirus, but the DNA genome is larger – 1,259,197 base pairs versus 1,182,000. The Megavirus genome encodes 1,120 putative proteins compared with 979 for Mimivirus. What is significant about Megavirus is that its genome resembles that of Mimivirus, including the presence of cellular genes such as those encoding amino-acyl tRNA synthetases. Also important is the fact that 258 of the Megavirus proteins have no counterparts in Mimivirus, including three amino-acyl tRNA synthetases.

When Mimivirus was first discovered, it was not clear if it was an anomaly, or if it would provide information on the emergence of viruses. Other giant viruses were subsequently discovered, but they were either nearly identical to Mimivirus (Mamavirus) or little genome sequence was available (Terra, Courdo, Moumou). The evolutionary distance of Megavirus and Mimivirus is sufficient to allow identification of similar features and the selection forces that lead to their emergence. A comparison of their DNA sequences reveals a set of genes in common between the two viruses, such as those that function during protein synthesis. These observations suggest that Megavirus and Mimivirus arose from a common cellular ancestor – one that could carry out protein synthesis – and lost the genes that were no longer needed. The alternative scenario, that these giant viruses started out small and acquired additional genes, seems unlikely. Seven different gene acquisition events would have been needed to acquire just the genes encoding amino-acyl tRNA synthetases.

More details about how Megavirus and Mimivirus emerged from a cellular ancestor will require the isolation of other giant DNA viruses. Which leads to the inevitable question – what is the biggest virus on earth? Have we reached the limit of viral genome size? Probably not, but I doubt that we will find viruses with much larger genomes that encode almost all the genes needed for independent replication. Such viruses likely evolved from primitive cells a very long time ago, and only the evolutionary descendants remain on Earth today.

If you are wondering how these giant viruses are named, the authors provide revealing background:

We believe it is useful and desirable that the name of a newly isolated microorganism convey some of its most distinctive properties. After the initial naming of Mimivirus (for “microbe mimicking”), already not a very good name because the prefix “mimi” does not convey a helpful scientific notion, newly isolated related viruses are receiving increasingly random/funny names such as “Mamavirus,” “Moumouvirus,” “Courdovirus,” and “Terra”. …we believe the current trend is counterproductive and should give way to more informative names….a distinctive feature of the above giant viruses (or of their close ancestors) is to possess genome in excess of a “megabase”. Hence, the term “Megavirus,” and the proposed family/genus “Megaviridae” that will be proposed… “Chilensis” then refers to the location where this virus was first isolated.

The authors did not incorporate the species of the viral host in the name of the virus. They justify this break with tradition because the natural host of  Megavirus chilensis is not known – it was isolated from the ocean by co-culture with acanthamoeba, a procedure the authors will continue to use to identify giant DNA viruses.

 Arslan D, Legendre M, Seltzer V, Abergel C, & Claverie JM (2011). Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae. Proceedings of the National Academy of Sciences of the United States of America, 108 (42), 17486-91 PMID: 21987820

  • Alan Dove

    I kind of liked the silly names. Oh, well.

    On a more serious (but highly theoretical) note, I wouldn’t dismiss the idea of finding much larger viruses. Evolution never stops, so it’s plausible that there could be a simple cellular parasite somewhere that’s just now undergoing the transition to virushood. The trick will be to catch it before it shrinks to Megavirus size, as it’s probably a “punctuated equilibrium” process. In other words, there might be some selective pressure favoring a rapid loss of genes down to a megabase or so, followed by a long stable period at that size. Given the short life cycles and rapid reproduction rates that are probably involved, the transition might be pretty abrupt.

  • http://www.virology.ws profvrr

    You might be right. I was not sure whether there exists a simple cellular organism that could serve as the origin of new giant DNA viruses. It’s the same problem with bacterial endosymbionts – you mainly see late states with many genes lost. There are intermediates discovered, but nothing near bacterial with almost complete genomes. We need to keep looking, but you can imagine that raising money to do this is also getting harder.

  • Dokerr

    Is there any special reason why these giant viruses have genes for aminoacyl tRNA synthetases? Can’t they use those of the host?

    Speculation: Would it be possible for a yet to be discovered virus to synthesize its own ribosomes? 
    ps The font size in the comments has shrunk recently – it’s now so small it hurts my eyes.

  • http://www.virology.ws profvrr

    Good question – the AA-tRNA synthetases have been expressed in E coli and the proteins have the expected activity. It is not known if they are expressed in virus infected cells, and if they are, whether they are needed for virus replication. A way to answer this question would be to delete the genes from the viral genome and see the effect on replication. Its not clear to me why such enzymes would be needed by the virus if they are also present in cells. Perhaps they are evolutionary remnants, genes from the viral ancestor not yet lost.

    I noticed the small comment fonts today and just fixed the problem.

  • Guest

    mikovits and ruscetti are back!!  http://www.cfsnovel.com/blog/?p=409&forumid=331851

  • Jen

    Is there something special about aminoacyl  tRNA  synthetases? Surely among the hundreds of genes these viruses have, there are others involved in doing things that most viruses don’t do, and yet its always these specific proteins that get singled out for mention in articles about the giant viruses- why?

  • http://www.virology.ws profvrr

    The aminoacyl tRNA synthetases have been give special attention because they are components of the translation apparatus never found before in any viral genome. Many of the recognizable Mimivirus genes have also been found in other large DNA viruses (DNA repair enzymes, topoisomerases, sugar, amino acid, and lipid modifying enzymes, glycosyl transferases). There are also a good number of Mimivirus genes with no known function, completely novel proteins. These don’t get any attention because no one know what they do.

  • http://twitter.com/Opiado Pablo Ramdohr

    Grande Chilito!!! Tenemos el Virus mas grandote del planeta! greetings form the Lab of Molecular Virology of the Pontificia Universidad Católica de Chile. GRANDE LOS VIRUS!!! y gracias por el Podcast que es Maravilloso!. ahhh yes, we listen your podcast from here.

  • http://www.virology.ws profvrr

    Gracias por su atención.

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  • Ariel

    Any updates on Pandoraviruse?

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