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  • Review Article
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Giant virus biology and diversity in the era of genome-resolved metagenomics

Nature Reviews Microbiology volume 20, pages 721–736 (2022)Cite this article

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Abstract

The discovery of giant viruses, with capsids as large as some bacteria, megabase-range genomes and a variety of traits typically found only in cellular organisms, was one of the most remarkable breakthroughs in biology. Until recently, most of our knowledge of giant viruses came from ~100 species-level isolates for which genome sequences were available. However, these isolates were primarily derived from laboratory-based co-cultivation with few cultured protists and algae and, thus, did not reflect the true diversity of giant viruses. Although virus co-cultures enabled valuable insights into giant virus biology, many questions regarding their origin, evolution and ecological importance remain unanswered. With advances in sequencing technologies and bioinformatics, our understanding of giant viruses has drastically expanded. In this Review, we summarize our understanding of giant virus diversity and biology based on viral isolates as laboratory cultivation has enabled extensive insights into viral morphology and infection strategies. We then explore how cultivation-independent approaches have heightened our understanding of the coding potential and diversity of the Nucleocytoviricota. We discuss how metagenomics has revolutionized our perspective of giant viruses by revealing their distribution across our planet’s biomes, where they impact the biology and ecology of a wide range of eukaryotic hosts and ultimately affect global nutrient cycles.

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Fig. 1: Timeline of important cultivation-dependent and cultivation-independent discoveries in the Nucleocytoviricota.
Fig. 2: Giant virus infection mechanisms and virion structures.
Fig. 3: Expansion of the Nucleocytoviricota phylogenetic diversity through metagenomics.
Fig. 4: Experimentally verified and computationally predicted host ranges of the Nucleocytoviricota.
Fig. 5: Predicted metabolic reprogramming of a giant virus-derived virocell and consequences of giant virus infection for host populations.

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Acknowledgements

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). The authors thank X. R. Chuan from the Department of Chemistry and Biochemistry, University of Texas, El Paso, USA, for providing 3D reconstruction images for AaV, mimivirus and CroV. The authors acknowledge R. Watanabe and K. Murata, ExCELLS, NINS, Japan, who provided 3D reconstruction image for medusavirus, R. N. Burton-Smith and K. Murata, ExCELLS, NINS, Japan, for cryo-electron micrographs of melbournevirus, and T. Klose, Department of Biological Sciences, Purdue University, USA, for the 3D reconstruction image for faustovirus.

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  1. DOE Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Frederik Schulz & Tanja Woyke

  2. Aix Marseille University, CNRS, IGS UMR7256, IMM FR3479, IM2B, IO, Marseille, France

    Chantal Abergel

  3. University of California Merced, Merced, CA, USA

    Tanja Woyke

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Glossary

Choanoflagellates

Small flagellated microeukaryotes that represent the closest known unicellular relatives of animals grouped together in a clade called Opisthokonta.

Viral factories

Transitory organelles developed by the virus in the cytoplasm of an infected host cell in which replication and assembly of giant viruses takes place.

Episome

A linear genetic element that can replicate independently of the host, and without integration into the host chromosome.

T number

The triangulation (T) number describes the number of structural units per face of the icosahedron and is calculated as the square of the distance between two adjacent fivefold vertices.

ORFans

Predicted genes without detectable homologues in public databases.

Corks

The distinctive structures of some virions; in the case of pithovirus, the cork is located at the apex of the viral particle and made of 15 nm-spaced stripes organized in a hexagonal honeycomb-like array.

Nucleosomes

Compact structural forms of DNA packed through binding at positively charged proteins.

Mini-metagenomics

Low complexity metagenomes generated from generally tens to hundreds of cell-sized particles.

Metacaspase

A multifunctional cysteine-dependent protease that, for example, plays a role in programmed cell death in eukaryotes.

Pan-genome

The combined set of genes within a defined selection of genomes.

Pseudogenization

A mechanism that leads to gene loss (functional genes become non-functional), most often through accumulation of mutations.

Hyaluronan synthase

An enzyme that facilitates the synthesis of cellular hyaluronan.

Rhodopsins

Pigment-containing proton pumps that convert light into a transmembrane electrochemical proton gradient.

Proto-eukaryote

A cell without membrane-bound organelles that is considered the ancestor of the eukaryotic cell.

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Schulz, F., Abergel, C. & Woyke, T. Giant virus biology and diversity in the era of genome-resolved metagenomics. Nat Rev Microbiol 20, 721–736 (2022). https://doi.org/10.1038/s41579-022-00754-5

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