Feature ACANTHAMOEBA ACANTHAMOEBA BOTTLE-SHAPED VIRUS; VIRUS; BOTTLE-SHAPED ACIDIANUS ; FREDERICK A. MURPHY/CDC GLOBAL ; FREDERICK A. MURPHY/CDC PLOS PATHOG. PLOS / ET AL. ; E. GHIGO J. VIROL. J. / ET AL. MIMIVIRUS. CENTRE ROW L–R: RABIES VIRUS; T4 BACTERIOPHAGE; ROTAVIRUS. BOTTOM ROW L–R: EBOLA VIRUS; TOBACCO RATTLE VIRUS; VIRUS; RATTLE TOBACCO EBOLA VIRUS; L–R: ROW BOTTOM ROTAVIRUS. T4 BACTERIOPHAGE; RABIES VIRUS; L–R: ROW CENTRE MIMIVIRUS. FALSE-COLOUR ELECTRON MICROGRAPHS (NOT TO SAME SCALE). TOP ROW L–R: SMALLPOX VIRUS; VIRUS; SMALLPOX L–R: ROW SCALE). TOP SAME TO (NOT MICROGRAPHS ELECTRON FALSE-COLOUR POLYPHAGA SPL; M. HÄRING HIV-2. Viruses come in all shapes and sizes, such as the giant mimivirus (top right) and the lunar-lander-shaped bacteriophage (centre). The incredible diversity of viruses They’re everywhere virologists look, and they’re not all bad. Scientists are beginning to identify and classify the nonillions of viruses on the planet and their contributions to global ecosystems. By Amber Dance 22 | Nature | Vol 595 | 1 July 2021 ©2021 Spri nger Nature Li mited. All rights reserved. ©2021 Spri nger Nature Li mited. All rights reserved. ya Breitbart has hunted novel time to be doing this kind of research, says part of a group whose members are large in viruses in African termite Breitbart. “I think, in many ways, now is the terms of both genome size and absolute size mounds, Antarctic seals and time of the virome.” (typically, 200 nanometres or more across). water from the Red Sea. But to In 2020 alone, the ICTV added 1,044 species These viruses infect amoebae, algae and other hit pay dirt, she has only to step to its official list, and thousands more await protists, putting them in a position to influ- into her back garden in Florida. description and naming. This proliferation of ence ecosystems both aquatic and terrestrial. Hanging around her swimming genomes prompted virologists to rethink the Schulz, now a microbiologist at the US pool are spiny-backed orbwe- way they classify viruses and helped to clarify Department of Energy Joint Genome Institute Mavers (Gasteracantha cancriformis) — strik- their evolution. There is strong evidence that in Berkeley, California, decided to search for ing spiders with bulbous white bodies, black viruses emerged multiple times, rather than related viruses in metagenome data sets. In speckles and six scarlet spikes that make them sprouting from a single origin. 2020, in a single paper3, he and his colleagues look like a piece of medieval weaponry. Even Even so, the true range of the viral world described more than 2,000 genomes from the more striking for Breitbart, a viral ecologist remains mostly uncharted, says Jens Kuhn, group that contains giant viruses; before that, at the University of South Florida in St Peters- a virologist at the US National Institute of just 205 such genomes had been deposited in burg, was what was inside. When she and her Allergy and Infectious Diseases facility at Fort public databases. colleagues collected a few spiders and ground Detrick, Maryland. “We really have absolutely Virologists have also looked inwards to them up, they found two viruses previously no idea what’s out there.” find new species. Viral bioinformatician Luis unknown to science1. Camarillo-Guerrero worked with colleagues Although we humans have been focused on Here, there and everywhere at the Wellcome Sanger Institute in Hinxton, one particularly nasty virus since early 2020, All viruses have two things in common: each UK, to analyse metagenomes from the human there are legions of other viruses out there encases its genome in a protein-based shell, and gut, and built a database containing more than waiting to be discovered. Scientists estimate each relies on its host — be it a person, spider 140,000 kinds of phage. More than half of these that there are about 1031 individual viral parti- or plant — to reproduce itself. But beyond that were new to science. Their study4, published in cles inhabiting the oceans alone at any given general pattern lie endless variations. February, matched others’ findings that one of time — 10 billion times the estimated number There are minuscule circoviruses with only the most common viruses to infect the bact- of stars in the known Universe. two or three genes, and massive mimiviruses eria in our guts is a group known as crAssphage It’s becoming clear that ecosystems and that are bigger than some bacteria and carry (named after the cross-assembly software that organisms rely on viruses. Tiny but mighty, hundreds of genes. There are lunar-lander- picked it up in 2014). Despite its abundance, they have fuelled evolution for millions of looking phage that infect bacteria and, of not much is known about how it contributes years by shuttling genes between hosts. In the course, the killer spiky balls the world is now to our microbiome, says Camarillo-Guerrero, oceans, they slice open microorganisms, spill- painfully familiar with. There are viruses that who now works at DNA-sequencing company ing their contents into the sea and flooding the store their genes as DNA, and others that use Illumina in Cambridge, UK. food web with nutrients. “Without viruses,” RNA; there’s even a phage that uses an alterna- Metagenomics has turned up a wealth of says Curtis Suttle, a virologist at the University tive genetic alphabet, replacing the chemical viruses, but it ignores many, too. RNA viruses of British Columbia in Vancouver, Canada, “we base A in the standard ACGT system with a aren’t sequenced in typical metagenomes, so would not be alive.” different molecule, designated Z. microbiologist Colin Hill at University College There are just 9,110 named species listed by Viruses are so ubiquitous that they can turn Cork, Ireland, and his colleagues looked for the International Committee on Taxonomy of up even when scientists aren’t looking for them in databases of RNAs, called metatran- Viruses (ICTV), but that’s obviously a pitiful scriptomes. Scientists normally use these data fraction of the total. In part, that’s because to understand the genes in a population that officially classifying a virus used to require are actively being turned into messenger RNA scientists to culture a virus in its host or host in to make proteins, but RNA virus genomes cells — a time-consuming if not impossible We really have can show up, too. Using computational tech- process. It’s also because the search has been absolutely no idea niques to pull sequences out of the data, the biased towards viruses that cause diseases team found 1,015 viral genomes in metatran- in humans or organisms we care about, such what’s out there.” criptomes from sludge and water samples5. as farm animals and crop plants. Yet, as the Again, they’d massively increased the number COVID-19 pandemic has reminded us, it’s of known viruses with a single paper. important to understand viruses that might Although it’s possible for these techniques jump from one host to another, threatening them. Frederik Schulz did not intend to study to accidentally assemble genomes that aren’t us, our animals or our crops. viruses as he pored over genome sequences real, researchers have quality-control tech- Over the past ten years, the number of from waste water. As a graduate student at niques to guard against this. But there are known and named viruses has exploded, the University of Vienna, in 2015 he was using other blind spots. For instance, viral species owing to advances in the technology for find- metagenomics to hunt for bacteria. This whose members are very diverse are fiendishly ing them, plus a recent change to the rules involves isolating DNA from a whole mix of difficult to find because it’s hard for computer for identifying new species, to allow naming organisms, chopping it into bits and sequenc- programs to piece together the disparate without having to culture virus and host. One ing all of them. A computer program then sequences. of the most influential techniques is metagen- assembles the bits into individual genomes; The alternative is to sequence viral genomes omics, which allows researchers to sample the it’s like solving hundreds of jigsaw puzzles one at a time, as microbiologist Manuel genomes in an environment without having whose pieces have been jumbled up. Martinez-Garcia does at the University of to culture individual viruses. Newer technol- Among the bacterial genomes, Schulz Alicante, Spain. He decided to try trickling ogies, such as single-virus sequencing, are couldn’t help but notice a whopper of a virus seawater through a sorting machine to isolate adding even more viruses to the list, includ- genome — obvious because it carried genes single viruses, amplified their DNA, and got ing some that are surprisingly common yet for a viral shell — with a remarkable 1.57 million down to sequencing. remained hidden until now. It’s an exciting base pairs2. It turned out to be a giant virus, On his first attempt, he found 44 genomes. Nature | Vol 595 | 1 July 2021 | 23 ©2021 Spri nger Nature Li mited. All rights reserved. ©2021 Spri nger Nature Li mited. All rights reserved. Feature VIRUS REALMS is entirely separate from the tree of cellular life, Unlike cell-based life forms, viruses don’t have a single common ancestor, which makes it impossible to create a included only the lower rungs of the evolution- phylogenetic tree. Instead, as of 2021, the International Committee on Taxonomy of Viruses recognizes six realms, ary hierarchy, from species and genus up to the defined by similarities in their members’ genes and proteins, each arising from a di erent common ancestor.