Making sense of the viral multiverse

In November 2019, probably, even earlier, a tiny entity measuring only a few hundred trillionths of a meter in diameter began tearing human society globally. Within months, the ruthless traveler known as SARS-CoV-2 had reached every populated corner of the earth, leaving scientists and health authorities with too many questions and few answers.

Today, researchers are struggling to understand where and how the new coronavirus arose, what features explain the puzzling constellation of symptoms it can cause, and how transmission wildfire can be controlled. An important part of this search will involve efforts to properly classify this emerging human pathogen and understand how it relates to other viruses that we can learn more about.

In a consensus statement, Arvind Varsani, a molecular virologist at the ASU Biodesign Center for Fundamental and Applied Microbiomies, and a host of international collaborators propose a new classification system, capable of locating coronaviruses such as SARS-CoV-2 within the huge network of viruses across the planet, known as the virosphere.

To adequately classify this staggering viral diversity, the group proposes a 15-range classification scheme and describes how three human pathogens – the severe acute respiratory syndrome coronavirus (SARS CoV), the Ebola virus, and the herpes simplex virus 1 – fit together. in the new frame of reference.

Varsani joins other elected executive members of the International Committee on Virus Taxonomy (ICTV), a fully volunteer organization of leading virologists from around the world, dedicated to designing a viable nomenclature to define viral species. Within ICTV, approximately 100 distinct task forces comprised of specialists from all the major viral families work to bring order to the tangled skein of elements in the virosphere.

The consensus statement appears in the online advanced edition of the magazine. Microbiology nature.

A closet of viruses

The new classification scheme, an elaboration of the previous binomial classification system devised by the great eighteenth-century taxonomist Carl Linnaeus, seeks to incorporate the full range of genetic divergence in the virosphere.

As a test case, the consensus statement shows how three human pathogens can be seamlessly incorporated into the new system. At the kingdom level, the lowest and most inclusive in the new taxonomy, two RNA viruses, the Ebola virus (EBOV) and the severe acute respiratory syndrome coronavirus (SARS-CoV) are grouped as ‘riboviria’, while herpes simplex 1, a double DNA virus, does not belong to the ribovirian kingdom, but is classified by five traditional ranges.

Designing an inclusive viral taxonomy is of great practical importance. It can play a vital role in the detection and identification of agents responsible for emerging epidemics in humans, livestock or plants. Establishing the taxonomic status of a virus allows clear and unequivocal communication between virologists and the scientific community in general.

“With viral metagenomic studies (involving the sequencing of genetic material recovered directly from the environment), we are discovering large numbers of viruses that we really can’t put in any particular order,” says Varsani. “We were tasked with trying to come up with a better taxonomic framework.” The new scheme is based in part on preserving key viral proteins and other properties that are among taxonomically related viruses for higher ranges.

The virus causing the current outbreak of coronavirus disease, for example, has recently been dubbed “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), after the ICTV Coronaviridae study group determined that the virus it belongs to the existing species, “severe acute coronavirus related to respiratory syndrome,” based in part on conserved proteins involved in the viral replication of SARS-CoV-2. (Earlier classifications of coronaviruses were largely based on serological reactivity studies with viral peak proteins, which give coronaviruses their characteristic club-like appearance.)

Visualizing the virosphere

Even for scientists used to dealing with extremely mind-boggling numbers, the virosphere is almost unfathomably vast. It has been estimated that 100 viruses could be assigned to each star in the entire universe without depleting the world’s supply, estimated at 1 million (or 1 followed by 30 zeros).

“One important thing about all of these frameworks for viral taxonomy is that they are dynamic. As we discover more viruses, things will have to change,” says Varsani. “And the same thing has happened in the floral kingdom, where people once classified plants based on petals, leaves, and other morphological characteristics. And soon, as genetic information entered, it contradicted people’s previous classification. These problems are common in the classification of plants, animals, fungi, and bacteria, and will certainly be very convincing to the initial proponents of that taxonomy. Perhaps a stark example is the misclassification of a plant as a daisy in the Asteraceae family, but of fact is a plant that imitates a daisy, because it wants a particular pollinator and genetically it is not part of Asteraceae “.

But the scope and genetic diversity of the viroma are just the beginning of the challenges facing researchers trying to develop a comprehensive taxonomy, a mega taxonomy, of the viral world. Viral lineages, for example, are exceptionally difficult to decipher. Unlike all cellular life on earth, viruses acquire their genomic material from many sources, a property known as polyphylogeny. Phenomena that include the horizontal transfer of genetic elements allow viruses to freely exchange elements of their identity, leaving researchers without a clear line of descent.

Furthermore, viral mutation rates are much faster and more prolific than their cell counterparts, due to poor error correction and genomic correction mechanisms, as well as the selective pressures that drive their relentless diversification.

Unity and diversity

Compared to other organisms, the diversity among viruses is extreme. They can differ in their genetic material (RNA or DNA) and in their basic structure (double or single chain), as well as in the orientation of their encoded genes. A further complication involves the fact that viral genomes can be distributed across separate units, sometimes packaged together in a virion, or into separate virus particles, all of which are necessary to infect a cell for replication to occur.

While all eukaryotes share a last common ancestor, distinct from bacteria and archaea, allowing researchers to trace their evolutionary origins and divergences to billions of years in the past, viruses lack a set of genes universally. conserved necessary to build an adequate phylogeny.

The new 15-range taxonomy is based on the 7-level Linnean system of kingdom, phylum, class, order, family, genus, species. It also borrows physiological elements from the so-called Baltimore taxonomy (developed by Nobel laureate David Baltimore). The Baltimore system also recognizes 7 levels, but is not hierarchical and uses variables including genome type and replication-expression strategies to guide viral classification.

The new taxonomy is an important step forward in the quest to bring the global organization to the viral world. Furthermore, despite the extreme diversity of evolutionary histories present in polyphyletic viruses, a unit is beginning to emerge that points to a primordial set of virus-like genetic elements. The entire subsequent history of life on earth can be read as a relentless dynamic between these selfish agents and their cellular hosts.

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