Classify Viruses — the Gain Is Worth the Pain Viruses Hold Solutions to a Lot of Problems, So Let’S Fund and Reward Cataloguing, Urge Jens H
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COMMENT Viruses that infect humans, such as Ebola, are a tiny fraction of what needs to be characterized. Classify viruses — the gain is worth the pain Viruses hold solutions to a lot of problems, so let’s fund and reward cataloguing, urge Jens H. Kuhn and colleagues. arth probably harbours a million been formally described. Comparative anal- single-stranded negative-sense RNA viruses times more virus particles than there yses of the genomes of these and numerous (see ‘Branching out’). Similar high-rank are stars in the observable Universe. unclassified viruses show that the current taxa could be established for other major EThese viruses could hold solutions to many taxonomy is vastly incomplete and, in places, virus groups. of humanity’s current problems. even wrong. Comprehensive classification of the Phage therapy could someday be used to Last month a momentous step was entire virosphere now seems within reach. treat diseases caused by multidrug-resistant announced by the International Commit- But major changes are needed to make that bacteria, for instance. Enzymes encoded by tee on Taxonomy of Viruses (ICTV), which happen. new viruses could help researchers to develop authorizes and organizes the classifica- OF HEALTH/SPL INSTITUTE NATIONAL pharmaceuticals. Or viruses that kill algal tion and naming of virus species. (Five of HIDDEN DIVERSITY cells could be used to control harmful blooms. us have roles in this organization: J.H.K., There are probably billions of distinct viruses. Tapping into the benefits — and threats — M.K., Y.-Z.Z., P.M. and V.V.D.) The com- Viruses depend on host cells to replicate, as do requires describing and cataloguing viruses mittee endorsed the establishment of taxa other ‘selfish’ genetic elements, such as viroids and mapping their evolutionary relationships. above the rank of order1. It introduced the and plasmids. The same host (say, humans or But, so far, just 4,958 virus species have first-ever virus phylum, Negarnaviricota, for the Escherichia coli bacterium) can be infected 318 | NATURE | VOL 566 | 21 FEBRUARY 2019©2019 Spri nger Nature Li mited. All ri ghts reserved. ©2019 Spri nger Nature Li mited. All ri ghts reserved. COMMENT by many, very different viruses. However, most of the viruses that have been described BRANCHING OUT infect only a few hosts. In fact, bacterial viruses (bacteriophages) often infect mem- A first for viruses bers of just one species, so are sometimes used to identify the bacteria in a sample. In other Higher taxonomic ranks of RNA viruses for single-stranded, negative-sense RNA words, the diversity of viruses is probably at can be established on the basis of a viruses. This single branch splits into two least as great as that of their available hosts. phylogeny of a universal marker. (In a subbranches, the subphyla Haploviricotina Only around 5,500 species of mammal and similar way, the taxonomy of cellular and Polyploviricotina (see ‘Classifying RNA about 391,000 species of vascular plant have organisms is based largely on the viruses’ and supplementary information). been established. But the smaller the organ- phylogenetic trees of universally conserved The need for two subphyla is also ism, the higher the numbers typically get. genes, such as those for ribosomal RNA.) supported by another major molecular There are 1 million to 10 million species of For RNA viruses, this marker is the RNA- marker. Haploviricotines synthesize a arthropod and probably more than 5.1 mil- dependent RNA polymerase (RdRp), the cap structure on virus messenger RNAs lion distinct fungi. And all bets are off when it only protein shared by all bona fide RNA that is required for protein synthesis comes to prokaryotes (bacteria and archaea). viruses. In the RdRp tree6, all negative- using a virus enzyme. Polyploviricotines, Estimates differ widely, but an analysis pub- sense RNA viruses form a single branch, by contrast, ‘snatch’ this cap from host lished earlier this month suggests that there justifying the phylum Negarnaviricota mRNAs. J.H.K. et al. could be as many as 1.6 million distinct 2 microbes on Earth . Each of these microbes CLASSIFYING RNA VIRUSES is almost certainly associated with at least Phylogenetic tree determined using RNA-dependent RNA polymerases. one virus. During one of the Tara Oceans expeditions BRANCH 2 (between 2009 and 2013), investigators iden- Includes poliovirus and BRANCH 4 SARS coronavirus. Includes Giardia tified 5,476 populations of double-stranded lamblia virus DNA viruses in 43 samples taken from 26 sta- and Colorado SOURCE: ADAPTED FROM REF. 6 FROM REF. SOURCE: ADAPTED BRANCH tick fever virus. tions. And only 39 of these populations were Includes Escherichia virus Qβ and found to closely resemble lineages recog- Ourmia melon virus. nized by the ICTV3. Only last year, a study of marine microbial metagenomes revealed more phylogenetic diversity in one proposed family of large DNA viruses (‘Megaviridae’) than currently exists in bacteria and archaea, Mobile genetic elements, 4 including non-long combined . terminal repeat (non-LTR) In short, the planet hosts massive virus retrotransposons. diversity. Subphylum UNTAPPED POTENTIAL BRANCH 3 Haploviricotina “So what?” some might ask. Only a few Includes hepatitis C virus Includes Ebola and tobacco mosaic virus. virus and hundred viruses are known to cause animal rabies virus. or plant diseases, and although more patho- genic viruses will certainly be discovered, they will probably number only in the hundreds. In our view, limiting analyses only to poten- Subphylum Polyploviricotina tially pathogenic viruses is short-sighted and BRANCH 5 Includes Lassa virus Phylum Negarnaviricota and inuenza A virus. ultimately negligent. Most antibiotics in The rst ever phylum is for single-stranded, clinical use were discovered from harmless negative-sense RNA viruses. soil bacteria. A key component of commer- cial detergents — heat-resistant proteases — was discovered in deep-sea prokaryotes not different from those they have access to today. fungi and worms that inhabit human bodies; known to harm any eukaryotes. Most influ- And bacterial and archaeal viruses encode those in our close associates — pets, pests ential biotechnological breakthroughs of the an enormous diversity of proteins that could and farm animals; and the viruses in the twentieth and twenty-first centuries are based enable geneticists to fine-tune their use of microfauna that inhabit these animals. on enzymes from seemingly ‘unimportant’ CRISPR to engineer organisms. Ultimately, we must decipher patterns in bacteria. Examples include: the restriction We cannot know what the trove of the virosphere — for instance, how viruses enzymes that launched genetic engineering ‘unimportant’ viruses could possibly amount interact with each other and with microbes, in the 1970s; the polymerase chain reaction to until we have examined them. as well as the triggers that cause them to jump (PCR) used to make many copies of a DNA What’s more, virologists are discovering hosts. Then, we might be able to predict the segment; and the CRISPR technology now that the phenomenon of switching hosts is emergence of the next HIV-1, Ebola virus, or revolutionizing genome engineering. Indeed, not as random and rare as was thought. Given influenza A virus that is capable of causing CRISPR–Cas systems were discovered the growing threat of emerging virus diseases another deadly pandemic. Antiviral therapy through the study of prokaryotic immune in the face of human-induced changes such could even be feasible for a person infected responses against viruses that no clinician as population growth, urbanization and cli- with a new virus, if researchers have a deep could name. mate change, describing and cataloguing the understanding of the virus’s closest relatives. It is quite possible that the proteases and viromes of healthy and sick humans is crucial. (A similar approach is now routinely used to polymerases encoded by the viruses of deep- Cataloguing should include all the viruses in treat bacterial infections.) sea organisms will offer researchers qualities human tissues; those in the bacteria, protists, Last but not least, comprehensive ©2019 Spri nger Nature Li mited. All ri ghts reserved. ©2019 Spri nger Nature Li mited. All ri ghts reserve21d. FEBRUARY 2019 | VOL 566 | NATURE | 319 COMMENT classification is essential for understanding functions almost exclusively through the as formal publications in their own right. Or how viruses and their cellular hosts have efforts of a few hundred volunteers who publishers could make submitting a proposal shaped each other, as well as how life on Earth advance virus taxonomy using their free to the ICTV a condition of publishing papers began and has evolved. time and, very often, personal funds. Thus, on newly described viruses (much of the the classification of viruses is somewhat information required for both is the same). MANY CHALLENGES neglected — especially for ones that do In principle, the classification of viruses could Classifying millions of viruses into not obviously fall under the purview of become routine, much the same as the depo- hierarchically organized taxa requires a the existing study groups or are discovered sition of gene-sequence information to public huge, community-wide effort and a broad through metagenomics surveys. databases such as GenBank has become com- array of researchers — including virologists, In 2017, the ICTV greatly eased the monplace in genomics. microbiologists, ecologists, veterinary sur- process by allowing viruses to be classified If more virologists joined ICTV study geons and zoologists. These scientists will on the basis of genome-sequence informa- groups, and all discoverers submitted taxo- need incentives. Changes should also be tion alone5. Before this, researchers had to nomic proposals and manuscripts in tandem, made to the classification process itself. grow and study them the specialists on the new viruses would rou- Currently, for a newly discovered virus or “The in the laboratory — a tinely join the ICTV volunteers in prepar- group of viruses to be classified, research- classification process that is feasible ing taxonomic proposals.