Researchers from the emerging tropical diseases research unit (Aix-Marseille University/CNRS/IRD/INSERM) – based in the Mediterranean Infection university hospital, with support from AP-HM (Marseilles hospitals grouping) – have demonstrated the existence of an immune system in giant viruses, able to prevent the infection of the latter by virophage viruses. A virophage is a virus that is capable of infecting other viruses. This is the first demonstration of an ‘immune’ system in viruses, to defend against other viruses. This work has recently been published in Nature.
The team led by Pr Didier Raoult was the first to report the existence of giant viruses (or giruses) in 2004 (Raoult et al. 2004). Mimivirus was the first giant virus discovered and, a few years later, the same team described a new entity: virophage viruses capable of infecting other viruses (La Scola et al. 2008). Since their discovery, giant viruses have revealed a number of unique characteristics that challenge the conventional definition of a virus, such as their large size, the size and complexity of their genome, the fact that they can be infected by virophage viruses and the presence of transpovirons (Desnues et al. 2012).
In the study published in Nature, the researchers observed that one group of Mimivirus (known as lineage A) developed resistance to infection by a virophage virus called Zamilon, whereas Mimivirus in lineages B and C were sensitive to infection by Zamilon. While attempting to understand this very specific, indeed unique, resistance mechanism, the researchers discovered the presence of a repeated DNA sequence in Zamilon that served to capture the virophage in lineage A only. This complex was named MIMIVIRE (MIMIvirus VIrophage Resistance Element) and demonstrated similar functions to the CRISPR-Cas defence system thought to exist only in bacteria and archaea, and containing one enzyme rolling out DNA and another cutting it.
Inactivation of the MIMIVIRE complex enabled restoration of Mimivirus sensitivity to virophage infection. Partner proteins found in this MIMIVIRE complex are involved in the specific deterioration of the foreign DNA. The MIMIVIRE viral defence system thus endows giant viruses with immunity, which been able to integrate the infectious virophage DNA into their genome.
This is the first demonstration that a virus can have an ‘immune’ system protecting against another virus, and reinforces the idea that there is a fourth world of microbes.