Giant viruses infecting amoebas, single-celled eukaryotic organisms, can themselves be parasitized by other viruses, called virophages, as well as mobile genetic elements called transpovirons, which are found in both categories of viruses.
In a study published in
Nature Communications, scientists have unraveled the interactions within this complex quadripartite system by analyzing the expression of their respective genes.
Virophages, viruses of viruses...
Viruses are often considered the ultimate parasites. However, some giant viruses infecting unicellular eukaryotes can themselves be parasitized by smaller viruses, known as virophages.
These virophages use the viral factory, a temporary organelle formed by the giant virus in the cytoplasm of the infected cell, to ensure their own replication.
This phenomenon constitutes a case of hyperparasitism, where a parasite is itself parasitized. Moreover, certain giant viruses and virophages carry DNA molecules in their particles in the form of episomes, called transpovirons. This system thus forms a network of complex interactions, involving a host cell, a giant virus, a virophage, and a transpoviron.
Controlled infection experiments to understand the underlying mechanisms
How is gene expression regulated for each partner during infection, and how is this regulation altered by the presence of others? To answer these questions, scientists conducted a series of controlled infection experiments by successively introducing the various actors.
They first studied the infection of the amoeba host
Acanthamoeba castellanii by the giant megavirus chilensis. They then proceeded with co-infections involving the virophage zamilon vitis, the transpoviron mvtv, and both at the same time. The transcriptome, that is, the total set of messenger RNAs, from each partner was analyzed through sequencing, allowing them to track the evolution of gene expression throughout the infectious cycle.
A fascinating theater of layered parasites
These analyses, published in the journal
Nature Communications, revealed that infection by the giant virus induces a profound alteration of the host cell's transcriptome, affecting nearly half of its genes. Although most are repressed, some are instead activated, enabling the virus to reshape the cell's metabolism to favor its replication.
Co-infection by the virophage significantly alters the expression of over a quarter of the giant virus's genes, with the majority being repressed, suggesting that the two viruses compete for the transcription machinery. However, this effect is transient and has no significant impact on the final production of giant virus particles.
An electron microscopy image of an [i]Acanthamoeba castellanii cell co-infected by the giant virus megavirus chilensis and the virophage zamilon vitis.
At the center of the image, in dark gray, one can see the viral factory, a structure present in the cell's cytoplasm where viral replication and the production of new particles of the giant virus (black arrows) and virophages (white arrows) take place.
© Lionel Bertaux, Sandra Jeudy, and Matthieu Legendre[/i]
This study also reveals that the presence of the virophage induces the overexpression of transcription factors encoded in the giant virus's genome. This is where the last partner, the transpoviron, comes into play. It exploits these changes to overexpress its own genes.
This quadripartite system illustrates the complexity of interactions between viruses, hosts, and mobile genetic elements. The amoeba, host to these viruses, is itself an opportunistic pathogen, placing us before a fascinating theater of layered parasites.
References:
Complex transcriptional regulations of a hyperparasitic quadripartite system in giant viruses infecting protists.
Bessenay A, Bisio H, Belmudes L, Couté Y, Bertaux L, Claverie JM, Abergel C, Jeudy S, Legendre M.
Nature Communications. October 9, 2024. DOI:
10.1038/s41467-024-52906-1.