The deciphering of the complete 1.2 Mb genome sequence of Acanthamoeba polyphaga Mimivirus sent a shock wave through the community of virologists and evolutionists. The size, gene content, and phylogenetic characterization of the virus genome challenged many accepted ideas about what virus should look like, and where they might come from.

Even though large DNA virus genome sequences accumulated steadily in the databases since the 1990s, Mimivirus represented a quantum leap by two accounts: quantitatively it was the first endowed with a gene content larger than cellular microorganisms (such as mycoplasmas), and qualitatively it was breaking the "conceptual mold" by exhibiting several genes coding for central components of the protein translation system, such as amino-acyl tRNA synthetases. Until then, protein translation was thought to be an absolute criterion distinguishing all cellular organisms from all types of viruses.

“The discovery of Mimivirus did for ever change the way biologists (and virologists) consider viruses.” “Our study shows that there is an overlap in term of particle dimension, genome size, and genetic complexity between the world of viruses and the world of cellular organisms.”

Despite its exceptional features, the Mimivirus genome was also found to harbor the characteristic core gene set of previously described large DNA virus families such as Poxviruses or Phycodnaviruses (algal virus). Mimivirus could thus be interpreted as some kind of "living fossil," suggesting that today’s large DNA viruses might have originated from ancestors as complex as primitive cellular organisms, by a process of reductive evolution (the progressive loss of genes, such as observed in intracellular parasitic bacteria).

Our paper thus revived a number of previously proposed theories on the origin of viruses, in particular those linking viruses to the emergence of the eukaryotic nucleus. This was clearly suggested by a controversial tree (published in Fig.3, that we fought very hard with the editor to retain in the final version of the paper) showing the lineage leading to Mimivirus branching very near the root of the eukaryotic lineages, as if it constituted a "4th domain of life."

  Does it describe a new discovery or a new methodology that’s useful to others?

The discovery of Mimivirus did forever change the way biologists (and virologists) consider viruses. For instance, it became difficult to hold the view that large DNA viruses (that we propose to call "Giruses" to distinguish them from regular tiny viruses such as RNA viruses) are not "living" organisms. The criteria of "filterability," used to distinguish bacteria that are retained on 0.3 micron-sized pore filters from viruses that are supposed to go through, is also invalidated. This has direct implication on experimental design in marine virology or in metagenomic studies.

Microbiologists specializing on the isolation of intra-cellular parasitic bacteria should now keep in the back of their mind that large DNA viruses might sometimes be mistaken for "uncultivable" micro-organisms. We believe the a priori size criteria used by environmental virologists probably precluded the discovery of many Mimivirus-sized "Giruses."

  Could you summarize the significance of your paper in layman’s terms?

Our study shows that there is an overlap in terms of particle dimension, genome size, and genetic complexity between the world of viruses and the world of cellular organisms. Furthermore, the finding of a partially functional protein translation apparatus in Mimivirus, and its position in the phylogenetic tree of life suggests that the largest DNA viruses could have emerged by a reductive evolution from an ancestral cell, soon after (or right before) the beginning of the eukaryotic lineage.

  How did you become involved in this research and were there successes or failures?

Our laboratory had a good experience in the genomics of intra-cellular bacteria, such as Rickettsia. Mimivirus was initially mistaken for an intracellular bacteria, but all attempts to identify it, or put it in culture were unsuccessful.

The sequencing of the genome went relatively smoothly, although its size was seriously underestimated, which caused some unforeseen delay in the completion of the work. Despite the numerous extraordinary features found in the Mimivirus genome, the paper was relatively quickly accepted, except for a strong resistance against the publication of the "tree of life" figure.

  Where do you see your research leading in the future?

We see ourselves isolating and characterizing more of these "Giruses" for which we already have evidence in various metagenomic data. This is important to determine if Mimivirus is just a freak evolutionary accident, or the first representative of a large population of viruses that were overlooked because of their unusual size and host range (e.g. marine protists).

Deciphering more of these extra-large virus genome sequences and comparing them should help resolve the current debate about the evolutionary origin of DNA viruses, and their implication in the emergence of the eukaryotic lineage.

  Are there any social or political implications of your research?

Definitely. Many of the genes identified in Mimivirus have totally unknown functions, although they are probably used to gain the control of the host’s cell metabolism. Elucidating the cellular functions of these viral genes could indicate new entry points for the control of the cell metabolisms.

New types of drugs could thus be developed to manipulate these pathways, opening new avenues in the therapy of proliferative or degenerative diseases. Mimivirus is also related to large DNA viruses controlling the populations of various planktons and micro-algae. These viruses may thus turn up to be of fundamental importance for regulating earth’s climate, and could be harnessed in our struggle against the threat of global warming.