Information Génomique et Structurale, Unité mixte de recherche CNRS - Aix Marseille Université, Institut de Microbiologie de la Méditerranée...

Our laboratory was created in 1995, by combining expertises in structural biology, genomics and bioinformatics. For the first ten years, we have been pioneers in the sequencing of many bacterial genomes [1, 2], in the field of structural genomics [3, 4] and in the development of the relevant bioinformatics tools [5], [6, 7]

Following our involvement in the characterization of the first “giant” virus (Mimivirus) in 2003 [8], [9], our laboratory quickly focused on the study of these new viruses, making the bet that Mimivirus was not an isolated evolutionary freak, but a first glance at a whole new virology area remained hidden because of historical biases in isolation protocols (namely filtration). Our intuition was also that through their astonishing properties, giant viruses (list in 2017) could shed new light on the emergence of the cellular world and its relationship with contemporary viruses [10, 11].

This change in direction was rewarded by the discovery of a multitude of more or less distant Mimivirus relatives, now forming the large family of Mimiviridae, some members of which play an essential role in the regulation of oceanic plankton populations [12, 13].
In parallel, the exploration of diverse environments quickly led us to the discovery of three other families of giant viruses (ie, visibles under the light microscope), without phylogenetic relationship with the Mimiviridae family. The prototypes of these three families are Pandoravirus salinus [14], Pithovirus sibericum [15] and Mollivirus sibericum [16]. The isolation of the last two viruses from a 30,000-year-old permafrost sample added a new concern to the potentially dreadful consequences of global warming.
While remaining in search of more giant viruses in the environment, our laboratory devotes an increasing part of its activity to the elucidation of the molecular and cellular processes accompanying the replication of the giant viruses [17], hence to the function of their genes, most of which have no counterpart in the contemporary cellular world [11].

In details

Our laboratory is a joint research unit CNRS-AMU. Our researches are mainly devoted to the discovery, the biology, the coping strategies and the evolution of “giant” viruses.

The discovery of Mimivirus, the first icosahedral virus visible by optical microscopy (~400 nm), was followed by the isolation and characterization of many members of the same family. The largest, {Megavirus chilensis}, has a genome of 1.2 Mb and encodes more than 1000 proteins, 2/3 of which are unique to the Mimiviridae. Megavirus is also the first marine virus from this family. Other members of the family, smaller and less complex, infect a variety of micro-algae and protozoa. As for the Poxviridae, their infectious cycle is cytoplasmic and they are themselves targeted by a new type of virus, the virophages, which replicates in the larger virus viral factory and not in the cell nucleus. Some are as episomes without capsids and are associated to the virus they infect packing their genome in the large virus’ virions.

During the past lastyears, our laboratory has discovered the three other giant virus families known today, the Pandoraviridae, with their unique amphora shaped virions morphologies (1 µm long for 0.5 diameters) are by far the most complex viruses, with genome sizes almost reaching 3Mb and encoding over 2550 proteins, 90% of which does not resemble any other in the cellular or the viral world. Yet we have already isolated more than 5 members of the Pandoraviridae and other laboratories start to isolate more.

{Pithovirus sibericum} was isolated from a Siberian permafrost samples dated 30,000 years old. It is by far the virus with the largest virions (1.5 microns, 0.5 microns in diameter). As Pandoravirus virions they are amphora-shaped but with totally different tegument and apex structures. With its only 610 kb genome only encoding 470 proteins it is the first time there is such decorelation between the genome and the virions sizes. Yet again, 2/3 of these proteins do not resemble anything known. The genome of another Pithovirus has just been published.

Finally, {Mollivirus sibericum} isolated from the same sample of permafrost has particles roughly spherical 600 nm in diameter. Its DNA genome of 650 kb encodes 520proteins 2/3 of which are unlike anything known.

We are also working on a new family of viruses infecting Acanthamoeba, the Marseilleviridae. These viruses are amazingly preserved from one place to another planet, whatever the backgrounds from which they were isolated to study the evolution and selection pressures on applying DNA virus genes in general. These viruses have also allowed us to identify an unsuspected evolutionary through addiction cell nucleus. They do not carry their DNA to the nucleus, instead they recruit nuclear proteins to compensate for lack of onboard transcription into virions and thus develop their viral factory in the cytoplasm. This is a missing link mode evolution cytoplasmic virus to a nuclear replication mode.

The skills of the laboratory initially centered on bioinformatics and structural genomics have gradually been extended to virology, cell biology and in an expertise in NGS data analysis (genomics, transcriptomics, metagenomics, proteomics) and light and electron microscopy in order to perform the detailed study of these viruses’ physiology.

One of the questions addressed by the discovery of these 4 families of giant viruses infecting Acanthamoeba is their origin. Where do these thousands of original proteins come from, what are their roles during the giant viruses’ infectious cycles which are for some of them cytoplasmic while others have a nuclear stage? Are they the remains of original metabolic pathways selected by ancestral proto-cells and not selected by LUCA (Last Universal Cellular Ancestor)? Could it be that life appeared several times on Earth, in parallel, and with different metabolic strategies? Some of these strategies may have led to the rapid emergence of the cellular world. We suggest that the alternative strategies were able to subsist, at least in part, in the descendants of these proto-cells that were the losers of the competition and could only survive by parasitizing the winners and thus became the viruses of the cellular world.