As more cases of COVID-19 are studied and treated worldwide, it had become apparent that the lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the ...SARS-CoV-2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings suggest de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a putative cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and help in designing assays to predict the virulence of naturally circulating SARS-like animal coronaviruses.
The right sampling of homologous sequences for phylogenetic or molecular evolution analyses is a crucial step, the quality of which can have a significant impact on the final interpretation of the ...study. There is no single way for constructing datasets suitable for phylogenetic analysis, because this task intimately depends on the scientific question we want to address, Moreover, database mining softwares such as BLAST which are routinely used for searching homologous sequences are not specifically optimized for this task.
To fill this gap, we designed BLAST-Explorer, an original and friendly web-based application that combines a BLAST search with a suite of tools that allows interactive, phylogenetic-oriented exploration of the BLAST results and flexible selection of homologous sequences among the BLAST hits. Once the selection of the BLAST hits is done using BLAST-Explorer, the corresponding sequence can be imported locally for external analysis or passed to the phylogenetic tree reconstruction pipelines available on the Phylogeny.fr platform.
BLAST-Explorer provides a simple, intuitive and interactive graphical representation of the BLAST results and allows selection and retrieving of the BLAST hit sequences based a wide range of criterions. Although BLAST-Explorer primarily aims at helping the construction of sequence datasets for further phylogenetic study, it can also be used as a standard BLAST server with enriched output. BLAST-Explorer is available at http://www.phylogeny.fr.
Mimivirus, a DNA virus infecting acanthamoeba, was for a long time the largest known virus both in terms of particle size and gene content. Its genome encodes 979 proteins, including the first four ...aminoacyl tRNA synthetases (ArgRS, CysRS, MetRS, and TyrRS) ever found outside of cellular organisms. The discovery that Mimivirus encoded trademark cellular functions prompted a wealth of theoretical studies revisiting the concept of virus and associated large DNA viruses with the emergence of early eukaryotes. However, the evolutionary significance of these unique features remained impossible to assess in absence of a Mimivirus relative exhibiting a suitable evolutionary divergence. Here, we present Megavirus chilensis, a giant virus isolated off the coast of Chile, but capable of replicating in fresh water acanthamoeba. Its 1,259,197-bp genome is the largest viral genome fully sequenced so far. It encodes 1,120 putative proteins, of which 258 (23%) have no Mimivirus homologs. The 594 Megavirus/Mimivirus orthologs share an average of 50% of identical residues. Despite this divergence, Megavirus retained all of the genomic features characteristic of Mimivirus, including its cellular-like genes. Moreover, Megavirus exhibits three additional aminoacyl-tRNA synthetase genes (IleRS, TrpRS, and AsnRS) adding strong support to the previous suggestion that the Mimivirus/Megavirus lineage evolved from an ancestral cellular genome by reductive evolution. The main differences in gene content between Mimivirus and Megavirus genomes are due to (i) lineages specific gains or losses of genes, (ii) lineage specific gene family expansion or deletion, and (iii) the insertion/migration of mobile elements (intron, intein).
Since 1998, when Jim van Etten's team initiated its characterization,
Chlorella virus 1 (PBCV-1) had been the largest known DNA virus, both in terms of particle size and genome complexity. In 2003, ...the
-infecting Mimivirus unexpectedly superseded PBCV-1, opening the era of giant viruses, i.e., with virions large enough to be visible by light microscopy and genomes encoding more proteins than many bacteria. During the following 15 years, the isolation of many Mimivirus relatives has made
one of the largest and most diverse families of eukaryotic viruses, most of which have been isolated from aquatic environments. Metagenomic studies of various ecosystems (including soils) suggest that many more remain to be isolated. As
members are found to infect an increasing range of phytoplankton species, their taxonomic position compared to the traditional
(i.e., etymologically "algal viruses") became a source of confusion in the literature. Following a quick historical review of the key discoveries that established the
family, we describe its current taxonomic structure and propose a set of operational criteria to help in the classification of future isolates.
DNA methylation is an important epigenetic mark that contributes to various regulations in all domains of life. Giant viruses are widespread dsDNA viruses with gene contents overlapping the cellular ...world that also encode DNA methyltransferases. Yet, virtually nothing is known about the methylation of their DNA. Here, we use single-molecule real-time sequencing to study the complete methylome of a large spectrum of giant viruses. We show that DNA methylation is widespread, affecting 2/3 of the tested families, although unevenly distributed. We also identify the corresponding viral methyltransferases and show that they are subject to intricate gene transfers between bacteria, viruses and their eukaryotic host. Most methyltransferases are conserved, functional and under purifying selection, suggesting that they increase the viruses' fitness. Some virally encoded methyltransferases are also paired with restriction endonucleases forming Restriction-Modification systems. Our data suggest that giant viruses' methyltransferases are involved in diverse forms of virus-pathogens interactions during coinfections.
Investigating the Concept and Origin of Viruses Nasir, Arshan; Romero-Severson, Ethan; Claverie, Jean-Michel
Trends in microbiology (Regular ed.),
12/2020, Letnik:
28, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The ongoing COVID-19 pandemic has piqued public interest in the properties, evolution, and emergence of viruses. Here, we discuss how these basic questions have surprisingly remained disputed despite ...being increasingly within the reach of scientific analysis. We review recent data-driven efforts that shed light into the origin and evolution of viruses and explain factors that resist the widespread acceptance of new views and insights. We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. We note that the philosophical aspects of virus evolution also impact the way we might prepare for future outbreaks.
The distinctions between virions and viruses and modern and ancient cells are crucial to understand virus origins and evolution.Viruses can be better defined by their generic features of genome propagation and dissemination rather than physical or biological properties of their virions or hosts.Virus genomes are characterized by the abundance of virus-specific genes that lack detectable cellular homologs. Despite their abundance, virus-specific genes are rarely discussed in the models of virus origin and evolution.The alignment-based methods are ill-suited for the origins of life research, especially when the objective is to place fast-evolving organisms or viruses in the tree of life.Protein structures may provide a better alternative to resolve the very deep branches in the tree of life.
The largest known DNA viruses infect Acanthamoeba and belong to two markedly different families. The Megaviridae exhibit pseudo-icosahedral virions up to 0.7 μm in diameter and adenine—thymine ...(AT)-rich genomes of up to 1.25 Mb encoding a thousand proteins. Like their Mimivirus prototype discovered 10 y ago, they entirely replicate within cytoplasmic virion factories. In contrast, the recently discovered Pandoraviruses exhibit larger amphora-shaped virions 1 μm in length and guanine—cytosine-rich genomes up to 2.8 Mb long encoding up to 2,500 proteins. Their replication involves the host nucleus. Whereas the Megaviridae share some general features with the previously described icosahedral large DNA viruses, the Pandoraviruses appear unrelated to them. Here we report the discovery of a third type of giant virus combining an even larger pandoravirus-like particle 1.5 μm in length with a surprisingly smaller 600 kb AT-rich genome, a gene content more similar to Iridoviruses and Marseillevirus, and a fully cytoplasmic replication reminiscent of the Megaviridae. This suggests that pandoravirus-like particles may be associated with a variety of virus families more diverse than previously envisioned. This giant virus, named Pithovirus sibericum, was isolated from a >30,000-y-old radiocarbon-dated sample when we initiated a survey of the virome of Siberian permafrost. The revival of such an ancestral amoeba-infecting virus used as a safe indicator of the possible presence of pathogenic DNA viruses, suggests that the thawing of permafrost either from global warming or industrial exploitation of circumpolar regions might not be exempt from future threats to human or animal health.
The extension of virology beyond its traditional medical, veterinary, or agricultural applications, now called environmental virology, has shown that viruses are both the most numerous and diverse ...biological entities on Earth. In particular, virus isolations from unicellular eukaryotic hosts (heterotrophic and photosynthetic protozoans) revealed numerous viral types previously unexpected in terms of virion structure, gene content, or mode of replication. Complemented by large-scale metagenomic analyses, these discoveries have rekindled interest in the enigma of the origin of viruses, for which a description encompassing all their diversity remains not available. Several laboratories have repeatedly tackled the deep reconstruction of the evolutionary history of viruses, using various methods of molecular phylogeny applied to the few shared "core" genes detected in certain virus groups (e.g., the
). Beyond the practical difficulties of establishing reliable homology relationships from extremely divergent sequences, I present here conceptual arguments highlighting several fundamental limitations plaguing the reconstruction of the deep evolutionary history of viruses, and even more the identification of their unique or multiple origin(s). These arguments also underline the risk of establishing premature high level viral taxonomic classifications. Those limitations are direct consequences of the random mechanisms governing the reductive/retrogressive evolution of all obligate intracellular parasites.
Abstract
Giant viruses are abundant in aquatic environments and ecologically important through the metabolic reprogramming of their hosts. Less is known about giant viruses from soil even though two ...of them, belonging to two different viral families, were reactivated from 30,000-y-old permafrost samples. This suggests an untapped diversity of
Nucleocytoviricota
in this environment. Through permafrost metagenomics we reveal a unique diversity pattern and a high heterogeneity in the abundance of giant viruses, representing up to 12% of the sum of sequence coverage in one sample.
Pithoviridae
and
Orpheoviridae
-like viruses were the most important contributors. A complete 1.6 Mb
Pithoviridae
-like circular genome was also assembled from a 42,000-y-old sample. The annotation of the permafrost viral sequences revealed a patchwork of predicted functions amidst a larger reservoir of genes of unknown functions. Finally, the phylogenetic reconstructions not only revealed gene transfers between cells and viruses, but also between viruses from different families.
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