Eukaryotic microorganisms differ from from prokaryotes (bacteria and archaebacteria) by the strict compartmentalization of their cell contents separating the nucleus, in which DNA replication and transcription into messenger RNA take place, and the cytoplasm, in which the ribosomes decode the messenger RNAs to synthesize the corresponding proteins. To initiate their replication, DNA viruses infecting eukaryotic cells (such as amoeba) must overcome this compartmen-talization. Until now, two different strategies were proposed:
- directly transport the viral genome into the nucleus of the host cell and use the cellular machinery (so-called "nuclear" viruses),
- implement viral transcription and replication machineries within the cytoplasm of the infected cell (so-called "cytoplasmic" viruses).

The characterization of the particle proteomes of several giant viruses, carried out by researchers at our laboratory and the Information Génomique et Structurale Laboratory (CNRS UMR7256, Marseille), challenged this traditional dichotomy. Indeed, although the viruses belonging to the Marseilleviridae family replicate in the cytoplasm and even if their genomes contain the genes encoding their own RNA polymerases, the analysis of the protein content of virions reveal that these machineries were undetectable in the viral particles. Thus, Marseilleviridae can not initiate their infectious cycle without the help of the RNA polymerases confined in the nucleus of the host they infect. The detailed study of the infectious cycle in amoeba of a new member of the Marseillesviridae family, Noumeavirus, demonstrate that the viral infection induces a temporary permeabilization of the nucleus of the host in the first minutes. This permeabilization then makes possible the recruitment of host nuclear enzymes necessary for the transcription of the viral early genes. Furthermore, an unexpected phenomenon was observed: the cell nucleus recovers its normal appearance after a few hours, while the multiplication of viral particles is at its peak in the cytoplasm.
These results highlight a new mode of viral replication observed for the first time with this new giant virus.

The discovery of such a remote control of the host nucleus has several consequences. This demonstrates the essential role played by proteomic analyzes, in addition to genomic analyzes, to explore the replication mode and evolution of giant double-stranded DNA viruses. Then, it opens new tracks to understand the mode of infection implemented by other large DNA viruses devoid of transcriptional apparatus but whose passage through the nucleus of the host cell has never been described. Finally, it allows to propose a model of reductive evolution of large DNA viruses in which initial cytoplasmic viruses have been able to engage in the gradual loss of their autonomy with respect to the nucleus, waiting to evolve towards the ability to carry their genome there.