Laboratory

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.

À la Une

"Des virus qui parasitent des virus géants qui infectent une cellule : des interactions complexes décryptées", nouvelle communication du CNRS

Les virus géants infectant les amibes, des organismes unicellulaires eucaryotes, peuvent être parasités par d’autres virus, les virophages, ainsi que des éléments génétiques mobiles appelés transpovirons et contenus dans les deux catégories de virus. Dans une étude publiée dans Nature Communications, des scientifiques ont décrypté les interactions au sein de ce système quadripartite complexe en analysant l’expression de leurs gènes respectifs.

Zombie viruses from the warming Arctic : Intervention de Jean-Michel Claverie "Science Foo camp (organized by O'Reilly, Digital Science, and Google)" le 27 juillet 2024, Churchill college, Cambridge, UK

Our research over the last ten years has reliably and reproducibly demonstrated that viruses can remain infectious after tens of thousands of years of freezing (48,000 years) in deep permafrost [1-3]. For obvious health safety reasons, our work was restricted to viruses infecting amoebae, but there is no reason why this conclusion could not be applied to other DNA viruses (classified in the same phylum, such as poxviruses, iridoviruses, or asfarviruses) causing diseases in humans or animals...

"Why ‘resurrection biology’ is gaining traction around the world" sur le site de CNN le 26/12/23

CNN Resurrection biology — attempting to bring strings of molecules and more complex organisms back to life — is gaining traction in labs around the world. The work is a far cry from the genetically engineered dinosaurs that escape in the blockbuster movie “Jurassic Park,” although for some scientists the ultimate goal is de-extinction and resurrecting animals and plants that have been lost. Other researchers are looking to the past for new sources of drugs or to sound an alarm about the possibility of long-dormant pathogens. The field of study is also about recreating elements of human history in an attempt to better understand how our ancestors might have lived and died. Here are four fascinating research projects in this emerging field that launched or made significant progress in 2023. Reviving ‘zombie’ viruses Warmer temperatures in the Arctic are thawing the region’s permafrost — a frozen layer of soil beneath the ground — and potentially stirring viruses that, after lying dormant for tens of thousands of years, could endanger animal and human health. Jean-Michel Claverie, a professor emeritus of medicine and genomics at the Aix-Marseille University School of Medicine in Marseille, France, is seeking to better understand the risks posed by what he describes as “zombie viruses” by resurrecting viruses from earth samples from Siberia.

"As Russia’s Permafrost Thaws, Ancient Pathogens Risk Re-Awakening" : Interview de Jean-Michel Claverie dans The Moscow Times

Ancient pathogens that have been preserved in northern Russia’s permafrost for millennia could reawaken as global temperatures rise, scientists warn, potentially putting humanity at risk of never-before-seen diseases. Jean-Michel Claverie, a virologist and emeritus professor at the Aix-Marseille University School of Medicine, is one of the few scientists worldwide who has studied “zombie viruses” in the Siberian permafrost. He warned they could be present in Russia’s frozen soil in a “very large number and diversity.”

"Zombie Viruses: Fascinating and a Little Frightening" sur le site WebMD Health News

March 10, 2023 – Of all the consequences of climate change, here’s one nobody counted on. A team of European researchers digging into Siberian permafrost discovered and revived 13 types of prehistoric viruses. As the ancient frozen ground slowly loses its “perma” label due to rising temperatures, more and more microbes that have never encountered modern humans are resurfacing...

Ces 8 virus anciens peuvent “ressusciter” si la glace éternelle fond. Nouvelles du monde du 30 juillet 2023

Le réchauffement climatique suscite de nouvelles inquiétudes chez les scientifiques. Ils craignent que le pergélisol qui a gelé pendant des années ne dégèle et libère les anciens virus piégés à l’intérieur. “Ce risque augmentera certainement dans le contexte du réchauffement climatique, où la fonte du pergélisol continuera d’augmenter, et davantage de personnes habiteront l’Arctique”, a déclaré Jean-Michel Claverie, biologiste informatique à l’Université d’Aix-Marseille en France qui étudie virus anciens et exotiques, cité par CNN, dimanche (30/7/2023).

"Virus zombies : que sont-ils et pourquoi représentent-ils un danger pour l'homme ?" Intervention de Jean-Michel Claverie dans le média italien wisesocietyit

En raison de la fonte de la glace causée par le changement climatique, certains virus et bactéries très anciens et apparemment éteints, piégés depuis des millénaires dans le pergélisol (la couche gelée du sol souterrain), pourraient se réveiller et donner vie à de nouvelles maladies inconnues et à la propagation de pandémies avant l'extinction des mammouths et des Néandertaliens. Parlons des soi-disant "virus zombies" !

Une nouvelle famille de protéines liant le fer et le soufre découverte dans les virus géants

Certains virus géants de la famille des Mimiviridae possèdent de petites protéines exceptionnellement riches en glycine et en cystéine incorporant des agrégats de fer et de soufre (Fe-S) sous forme d’architectures de type [2Fe-2S] et [3Fe-4S] linéaire, cette dernière étant extrêmement rare dans le vivant. Ces protéines Fe-S sont très abondantes dans les particules virales et probablement essentielles pour l’infection. Ces travaux exploratoires, publiés dans la revue JACS, permettent d’aborder la question du rôle des centres Fe-S en virologie, un domaine quasiment inexploré à ce jour.

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