Periodic Reporting for period 1 - CHIMERA (The sympatric lifestyle of giant viruses: contact tracing and fitness through mobile genetic elements)
Berichtszeitraum: 2023-07-01 bis 2025-12-31
Giant viruses appear to be ubiquitous in soil and aquatic environments, infecting a wide range of protist hosts. As lytic viruses, they are important regulators in nutrient and energy cycles and key influencers of microbial community composition. The discovery of giant viruses challenged previous assumptions and blurred the sharp division between viruses and cellular life. Besides large particle sizes, giant viruses possess complex “chimeric” genomes, including genes likely acquired from their hosts and from bacteria that parasitise the same hosts. Unique is the presence of prokaryotic-like mobile genetic elements (MGEs) that are speculated to aid giant viruses in defence against the host immune response or in direct competition with other viruses or bacteria for resources. Conversely, bacteria may use MGEs to help hosts counter viral infections. The factors promoting giant virus diversity and maintenance of the virus-host balance in nature are largely unknown.
Mobile genetic elements (MGEs) are abundant in cellular genomes, but are very rare within viruses infecting eukaryotes. Thus, the presence of prokaryotic-like MGEs in giant virus genomes is a unique feature. Like viruses, MGEs are considered selfish genetic elements that tend to act as molecular parasites within the genomes in which they reside. They can move within and between genomes, even between genomes of different organisms. Together with viruses, MGEs are considered important drivers of genome evolution that have contributed to major evolutionary transitions, such as the origin of prokaryotic and then eukaryotic cells. MGEs can also play an important role in host-parasite co-evolution, in which the same molecular systems are employed by hosts and parasites for defence and subsequent counter-defence, thereby tightly linking the evolution of MGEs and defence systems. The role of MGEs in giant viruses is so far unknown. Following the yet-to-be-tested molecular symbiosis hypothesis, there is a mutual beneficial association between MGEs and giant viruses, where MGEs provide mobility to viral genes and aid viruses in defence against the host immune response and/or other competing parasites, and in turn, giant virus genomes provide a safe haven for MGEs, ensuring their persistence in nature.
In the proposed project, we investigate the role of MGEs in the evolution and ecology of giant viruses. The central hypothesis of this project is that MGEs play a crucial role in the competition between giant viruses and other parasites infecting the same hosts. When competing directly for resources, the presence of MGEs in giant virus genomes may confer higher viral fitness. In turn, other parasites, such as bacteria, may use similar MGEs as a counter-defence, creating a constant flux of MGEs as defence systems.
The main objectives are:
1. Genetic modification of giant virus genomes
2. Understand the role of MGEs in giant virus genomes.
3. Better understand how giant viruses interact with other viruses, their hosts, bacterial symbionts the host harbours, and bacteria on which the host feeds.
4. Trace the evolutionary history of giant viruses through contact tracing using MGEs.
Using co-infection experiments and cutting-edge molecular, microscopy, and sequencing techniques, we will investigate viral competitive fitness and physical and molecular interactions between selected partners. By genetically modifying giant virus genomes, we will test whether MGEs confer a fitness advantage. Moreover, we will combine cell sorting with metagenome analysis of selected habitats to unravel how MGEs are distributed in different ecosystems. The overarching goal is to use MGEs to investigate the evolutionary history of giant viruses and to elucidate the molecular dialogue among this unique group of viruses, bacteria, and their hosts.
Mobile genetic elements (MGEs) are abundant in cellular genomes, but are very rare within viruses infecting eukaryotes. Thus, the presence of prokaryotic-like MGEs in giant virus genomes is a unique feature. Like viruses, MGEs are considered selfish genetic elements that tend to act as molecular parasites within the genomes in which they reside. They can move within and between genomes, even between genomes of different organisms. Together with viruses, MGEs are considered important drivers of genome evolution that have contributed to major evolutionary transitions, such as the origin of prokaryotic and then eukaryotic cells. MGEs can also play an important role in host-parasite co-evolution, in which the same molecular systems are employed by hosts and parasites for defence and subsequent counter-defence, thereby tightly linking the evolution of MGEs and defence systems. The role of MGEs in giant viruses is so far unknown. Following the yet-to-be-tested molecular symbiosis hypothesis, there is a mutual beneficial association between MGEs and giant viruses, where MGEs provide mobility to viral genes and aid viruses in defence against the host immune response and/or other competing parasites, and in turn, giant virus genomes provide a safe haven for MGEs, ensuring their persistence in nature.
In the proposed project, we investigate the role of MGEs in the evolution and ecology of giant viruses. The central hypothesis of this project is that MGEs play a crucial role in the competition between giant viruses and other parasites infecting the same hosts. When competing directly for resources, the presence of MGEs in giant virus genomes may confer higher viral fitness. In turn, other parasites, such as bacteria, may use similar MGEs as a counter-defence, creating a constant flux of MGEs as defence systems.
The main objectives are:
1. Genetic modification of giant virus genomes
2. Understand the role of MGEs in giant virus genomes.
3. Better understand how giant viruses interact with other viruses, their hosts, bacterial symbionts the host harbours, and bacteria on which the host feeds.
4. Trace the evolutionary history of giant viruses through contact tracing using MGEs.
Using co-infection experiments and cutting-edge molecular, microscopy, and sequencing techniques, we will investigate viral competitive fitness and physical and molecular interactions between selected partners. By genetically modifying giant virus genomes, we will test whether MGEs confer a fitness advantage. Moreover, we will combine cell sorting with metagenome analysis of selected habitats to unravel how MGEs are distributed in different ecosystems. The overarching goal is to use MGEs to investigate the evolutionary history of giant viruses and to elucidate the molecular dialogue among this unique group of viruses, bacteria, and their hosts.
To study giant virus interactions under the microscope, we have successfully developed and applied a giant virus FISH protocol. The results of this study have been published in Journal of Virology (Mayer et al. 2025) and led to a collaboration with an international laboratory where we show that giant viruses create subcellular compartments to overcome codon-tRNA mismatches (Zhang et al. 2024). Unexpectedly, the results of this study led to a better understanding of the giant virus replication cycle and how virus genome complexity influences virus-host interactions.
To better understand the host response to viral infection (and other virus-host interactions), we have sequenced the genomes of six amoeba hosts that we commonly use in the laboratory to study giant viruses. The results of this study have been published in Genome Biology and Evolution (Willemsen et al. 2024). The host genomes are essential for pursuing the rest of the project.
To better understand the host response to viral infection (and other virus-host interactions), we have sequenced the genomes of six amoeba hosts that we commonly use in the laboratory to study giant viruses. The results of this study have been published in Genome Biology and Evolution (Willemsen et al. 2024). The host genomes are essential for pursuing the rest of the project.
Although most viruses replicate in the host cell’s nucleus, the giant Mimivirus replicates in viral factories established in the host cell’s cytoplasm. Before our study (Mayer et al. 2025), the location of the various steps in the Mimivirus replication cycle was largely unknown. By developing new protocols to label giant virus mRNA, protein synthesis, host cell membranes and rRNA, we demonstrate that Mimivirus transcription occurs at well-defined sites within the viral factory. In contrast, translation occurs directly outside it. This is different from other viruses known to have a cytoplasmic life cycle. These results bring us a step closer to understanding how viral genome complexity influences virus-host interactions and viral replication strategies.