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Gorbalenya, A. E.

Publications and source records attributed to Gorbalenya, A. E..

4 recordsLinked to original sources

A large replicase of nidovirus-like complexity in a putative RNA virus order "Quisvirales" expands the known diversity of helicase superfamilies

Helicases are essential ATPases that unwind nucleic acids and are classified into six recognized superfamilies (SF1-SF6). All positive-stranded RNA viruses (ssRNA+) with genomes larger than [~]7 kb encode SF1-SF3 helicases, linking them to RNA genome expansion. In the phylum Pisuviricota that includes many pathogens, helicases of SF1-SF3 are integrated into multi-enzyme replicases including 3C(-like) proteases (3CLpro) and RNA-dependent RNA polymerases (RdRp). Here, large-scale mining of invertebrate metastranscriptomes uncovered six related spider-associated ssRNA+ viruses that, based on their conserved 3CLpro-RdRp module, genome size (20-22 kb), and phylogeny, form a putative new order, "Quisvirales". Quisviruses have similar genome and replicase architectures to enveloped coronaviruses and other nidoviruses. However, the nidovirus SF1 helicase is replaced in quisviruses by a novel superfamily helicase that, like the Picornavirales SF3 helicase, comprises an AAA+ (ATPase-like) domain. Thus, viruses with large replicases of nidovirus-like complexity may have evolved repeatedly from an 3CLpro-RdRp-encoding ancestor.

microbiology↗

RNA genome expansion up to 64 kb in nidoviruses is host constrained and associated with new modes of replicase expression

Positive-strand RNA viruses of the order Nidovirales with genomes larger than [~]20 kb, including the largest known 36.7 kb RNA genome in vertebrate viruses, encode a proofreading exoribonuclease (ExoN). Here, we assemble 76 genome sequences of invertebrate nidoviruses from >500.000 published transcriptome experiments and triple the number of known nidoviruses with >36 kb genomes, including the largest known 64 kb RNA genome. We classify multi-cistronic ExoN-encoding nidoviruses into five groups, according to canonical and non-canonical modes of viral polymerase expression by ribosomes and genome segmentation. The largest group employing the canonical mode comprises invertebrate and vertebrate nidoviruses, including coronaviruses, with genomes ranging from 20-to-36 kb. Four groups with non-canonical expression modes include giant invertebrate nidoviruses with 31-to-64 kb genomes, some of which utilize dual ribosomal frameshifting that we validate experimentally. Thus, expansion of giant RNA virus genomes, the vertebrate/invertebrate host division, and the control of viral replicase expression are interconnected.

microbiology↗

Deep mining of the Sequence Read Archive reveals bipartite coronavirus genomes and inter-family Spike glycoprotein recombination

Genetic variation in RNA viruses is generated by point mutation and recombination as well as reassortment in the case of viruses with segmented genomes. While point mutation concerns only few sites per genome copy, recombination and reassortment can affect large genome regions, possibly facilitating the sudden emergence of novel traits. The contribution of recombination and reassortment to genomic plasticity and their rates remain poorly understood and might be underappreciated because of the lack of a comprehensive description of the virosphere. Here we employed a computational approach that directly queries primary sequencing data in a highly parallelized way and involves a targeted viral genome assembly strategy. By screening more than 213,000 data sets from the Sequence Read Archive repository and using two metrics that quantitatively assess assembly quality we discovered 25 novel nidoviruses from a wide range of vertebrate hosts. These include eight fish coronaviruses with bipartite genomes, a giant 36.1 kilobase coronavirus genome with a duplicated Spike glycoprotein (S) gene, and 16 additional so far undescribed vertebrate nidoviruses. Some of these novel virus genomes encode protein domains that have not been described for nidoviruses. We provide evidence for a possible inter-family homologous recombination event involving S between ancestral bipartite coronaviruses and unsegmented tobaniviruses and report a case example of an individual fish simultaneously infected with members from both virus families. Our results shed light on the evolution and genomic plasticity of coronaviruses and identify recombinants with a possibly improved ability to cross species barriers, which might elevate their pandemic potential.

microbiology↗

Severe acute respiratory syndrome-related coronavirus - The species and its viruses, a statement of the Coronavirus Study Group

The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

microbiology↗