Sequence-based studies — from metagenomics to single-cell work — have quickly accelerated understanding of giant viruses.
In the last thirty years, in environments all over the world, scientists have discovered giants among viruses. Now categorized in their own phylum, Nucleocytoviricota, these giant viruses boast larger genomes than many bacteria. Until recently, understanding of giant viruses came primarily from sampling an environment, then co-culturing isolated viruses in eukaryotic microbial hosts. Lately, researchers have used culture-independent approaches to gain insight into the genomes of giant viruses. In a new review, researchers from the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), and Aix Marseille University located in Marseille, France, leverage their experience to provide a perspective on giant virus diversity, and how sequencing and bioinformatics have sped up the study of giant viruses.
In their existence as large, cosmopolitan, and complex parasites, giant viruses often infect microeukaryote hosts. In doing so, they influence ecosystem-level nutrient cycling and carbon storage. For example, the marine algae Emiliania huxleyi, a microeukaryote, forms large algal blooms in the ocean that cycle environmental carbon and sulfur. A giant virus, the E. huxleyi virus, plays a key role in those cycles, as well. When the virus infects a bloom of E. huxleyi, it bursts the algal cells like water balloons, releasing vast amounts of calcite and nutrients back into the ocean. Because other giant viruses live globally and infect diverse microeukaryotes, it is likely that they influence similar nutrient cycles in various environments around the world.
In this review, researchers Schulz, Abergel and Woyke summarize insights from three decades of work on giant viruses. Isolating and co-cultivating these viruses has enabled findings on host range, morphological structures, and infection strategies. More recently, employing cultivation-independent approaches has yielded discovery of thousands of new giant viruses, rapidly expanding the diversity of the Nucleocytoviricota phylum.
As a group, giant viruses infect a wide array of microeukaryotes, from algae to heterotrophic protists, as well as animals. Giant virus morphology spans from very large virions (700 nm in diameter) to much smaller virions (120 nm in diameter). Across the phylum Nucleocytoviricota, diversity exists in infectious cycles, as well, with viruses relying on different strategies for initiation, replication and exit of host cells.
Leveraging culture-independent methods, researchers have shed light on the genetic makeup of new giant viruses. This review highlights four of these approaches. One way of detecting giant viruses in sequence data is read-mapping: using giant virus reference genomes to search for giant viruses in metagenomic reads. Another approach, single cell methods — involving flow cytometry and sequencing of single viruses or single host cells harboring them — could be a future option to discovering giant viruses. Further, single-marker gene based surveys allow researchers to use signature genes, rather than an entire reference genome, to sift for snippets of giant viruses in metagenomes. This has been useful in marine environments, where it has become clear that viruses are more abundant than previously thought, and potentially even more abundant than bacteria. A fourth option for virus discovery is reconstructing metagenome-assembled genomes through metagenomic binning. So far, this has been the most productive approach for giant virus genomic discovery. In 2020, a JGI-led team used this approach to deliver novel viral genomes from freshwater, sewage, and marine samples.
In addition to highlighting many viruses simultaneously, these genomic studies provide information about virus hosts. As a result, the outcomes of these studies have quickened the pace of understanding these viruses via their genomes, paving the way for future targeted isolation efforts and subsequent detailed experimental studies — ultimately, aimed at understanding how these giant viruses might affect global biogeochemical cycles.
Ramana Madupu, Ph.D.
Biological Systems Sciences Division
Office of Biological and Environmental Research
Office of Science
US Department of Energy
Tanja Woyke and Frederik Schulz
DOE Joint Genome Institute
email@example.com and firstname.lastname@example.org
This work was conducted by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, under contract no. DE-AC02–05CH11231. C.A. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 832601).
- Schulz, F., Abergel, C. & Woyke, T. “Giant virus biology and diversity in the era of genome-resolved metagenomics.” Nat Rev Microbiol (2022). doi: https://doi.org/10.1038/s41579-022-00754-5
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