Viruses upon viruses


Mimivirus. From Mimiviridae.


So, naturalists observe, a flea
Has smaller fleas that on him prey;
And these have smaller still to bite ’em;
And so proceed ad infinitum.

--Jonathan Swift, 1733, On Poetry, a Rhapsody

I've commented before on the hazards of making generalisations in biology, because no sooner do you think you've found a hard and fast rule than something comes along to break it. Seemingly basic questions have a way of becoming insanely difficult. Such as how do we decide whether or not something is alive? It may seem obvious at first glance - you may be fully confident that you yourself are alive, while the bloated gaseous corpse of a particularly unfortunate raccoon is most definitely not alive*. However, in making this argument you are glossing over the point that you are only considering extremes on the spectrum - as one gets closer and closer to the border between "alive" and "not alive", you may find it harder to confidently assign something to one or the other of your supposedly exclusive categories. Viruses have long been a classic example of such a difficult prospect. Viruses reproduce and disperse like more standard living organisms, but are generally regarded as not alive they do not do so independent of their host (but then, arguably neither do intracellular parasites such as Chlamydia and Microsporidia), and indeed they have to integrate themselves fully into their host's genome as part of doing so (which, admittedly, Chlamydia and Microsporidia do not). Is a virus alive or not alive? To what extent, if any, does it even make a difference?

*It's when I use phrases such as "bloated gaseous corpse" that it becomes obvious that I read way too much Mervyn Peake in my youth**.

**Not my misspent youth, I should point out. I tried to misspend it, but I don't think I ever really got the hang of misspending.

A few years ago, this still didn't seem like that much of an issue. Because viruses do not maintain a separate organismal identity throughout their reproductive cycle, it may be easier to imagine them as independently dispersing genetic fragments rather than discrete organisms in their own right. But then Mimivirus came along and, to use Scott Adams' phrase, demanded a "paradigm shift without a clutch". Mimivirus, a parasite of the amoebozoan Acanthamoeba, was the largest known virus to date when first described in 2003 (La Scola et al., 2003). So large is it that it is actually visible using an optical microscope and was apparently originally mistaken for a bacterium. When Mimivirus first infects its host, it releases its genetic material into the host cytoplasm. The viral DNA travels into the host nucleus (where it may or may not begin replicating) before travelling out again and inducing the formation of a separate "viral factory" that produces the progeny viruses (Suzan-Monti et al., 2007). However, with a genome of some 1.2 million base pairs, Mimivirus carries considerably more genetic material than many parasitic prokaryotes. It even carries genes to produce its own translation RNAs (Raoult et al., 2004). Phylogenetic analysis of the Mimivirus tRNA genes gave a position on the eukaryote stem outside the three standard domains of living organisms, leading to the implication that this might be some sort of surviving "progenote" (though I am personally skeptical - Mimivirus is different enough from prokaryotes and eukaryotes that even if the analysis is theoretically valid, long-branch effects are bound to be an issue). If Mimivirus is to be dismissed as not an organism in its own right, then it is as close to being one as one can possibly get, and trying to argue for either possibility carries a distressingly high risk of brain implosion.

A paper currently sitting in the advance online section of Nature (La Scola et al., in press 2008) carries the confusion even further. The authors of the paper were investigating a newly-discovered close but even larger relative of Mimivirus that they had dubbed Mamavirus in view of its size. In the process of doing so, they noticed a much smaller virus in association with Mamavirus that was eventually dubbed Sputnik. At first, Sputnik was assumed to be another Acanthamoeba pathogen, but further investigation established that Sputnik would only replicate in amoeboids that were also infected with mimivirids. In fact, Sputnik replicates in the mimivirid viral factories. Its presence is associated with the production of misformed mimivirids, and causes a 70% reduction in production of infectious Mimivirus. The conclusion of the researchers is unprecedented but almost inevitable - Sputnik is a virus that parasitises another virus.

Of course, it's not so simple and straightforward. Perhaps one could argue that Sputnik is not so much attacking the Mimivirus directly as hijacking the replicative framework produced by the amoebozoan host that the Mimivirus is inducing. But then, one could make similar (and perhaps similarly facetious) arguments about almost any case of hyperparasitism involving more unequivocal living organisms, or many other trophic relationships - if a lion kills a zebra then eats the zebra's stomach and intestines, is it eating the zebra or the grass ingested by the zebra? If there is one rule in biology, it is that life does not take kindly to clear-cut definitions.

More has been written on the Sputnik virus at Living the Scientific Life.

REFERENCES

La Scola, B., S. Audic, C. Robert, L. Jungang, X. de Lamballerie, M. Drancourt, R. Birtles, J.-M. Claverie & D. Raoult. 2003. A giant virus in amoebae. Science 299: 2033.

La Scola, B., C. Desnues, I. Pagnier, C. Robert, L. Barrassi, G. Fournous, M. Merchat, M. Suzan-Monti, P. Forterre, E. Koonin & D. Raoult (in press, 2008) The virophage as a unique parasite of the giant mimivirus. Nature.

Raoult, D., S. Audic, C. Robert, C. Abergel, P. Renesto, H. Ogata, B. La Scola, M. Suzan & J.-M. Claverie. 2004. The 1.2-megabase genome sequence of Mimivirus. Science 306: 1344-1350.

Suzan-Monti, M. B. La Scola, L. Barrassi, L. Espinosa & D. Raoult. 2007. Ultrastructural characterization of the giant volcano-like virus factory of Acanthamoeba polyphaga Mimivirus. PLoS ONE 2(3): e328.

1 comment:

  1. Oddly, I had that Swift verse in my head when I woke up this morning, inspired, I guess, by getting attacked by a lacewing larva yesterday...

    ReplyDelete

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