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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has shown a remarkable capacity to adapt and evade human immune responses and increase its human-to-human transmissibility. The genome of SARS-CoV-2 is also increasingly scarred by the effects of multiple C→U mutations from host genome editing as a cellular defense mechanism akin to restriction factors for retroviruses. Through the analysis of large data sets of SARS-CoV-2 isolate sequences collected throughout the pandemic period and beyond, we show that C→U transitions have driven a base compositional change over time amounting to a net loss of C bases and accumulation of U’s at a rate of approximately 0.2%–0.25%/decade. Most C→U substitutions occurred in the absence of the preferred upstream-base context or targeting of unpaired RNA bases previously associated with the host RNA editing protein, APOBEC 3A. The analyses provide a series of testable hypotheses that can be experimentally investigated in the future.

Background There is an increasing need to develop bioinformatic tools to organise and analyse the rapidly growing amount of nucleotide and amino acid sequence data in organisms ranging from viruses to eukaryotes. Finding A simple sequence editor (SSE) was developed to create an integrated environment where sequences can be aligned, annotated, classified and directly analysed by a number of built-in bioinformatic programs. SSE incorporates a sequence editor for the creation of sequence alignments, a process assisted by integrated CLUSTAL/MUSCLE alignment programs and automated removal of indels. Sequences can be fully annotated and classified into groups and annotated of sequences and sequence groups and access to analytical programs that analyse diversity, recombination and RNA secondary structure. Methods for analysing sequence diversity include measures of divergence and evolutionary distances, identity plots to detect regions of nucleotide or amino acid homology, reconstruction of sequence changes, mono-, di- and higher order nucleotide compositional biases and codon usage. Association Index calculations, GroupScans, Bootscanning and TreeOrder scans perform phylogenetic analyses that reconcile group membership with tree branching orders and provide powerful methods for examining segregation of alleles and detection of recombination events. Phylogeny changes across alignments and scoring of branching order differences between trees using the Robinson-Fould algorithm allow effective visualisation of the sites of recombination events. RNA secondary and tertiary structures play important roles in gene expression and RNA virus replication. For the latter, persistence of infection is additionally associated with pervasive RNA secondary structure throughout viral genomic RNA that modulates interactions with innate cell defences. SSE provides several programs to scan alignments for RNA secondary structure through folding energy thermodynamic calculations and phylogenetic methods (detection of co-variant changes, and structure conservation between divergent sequences). These analyses complement methods based on detection of sequence constraints, such as suppression of synonymous site variability. For each program, results can be plotted in real time during analysis through an integrated graphics package, providing publication quality graphs. Results can be also directed to tabulated datafiles for import into spreadsheet or database programs for further analysis. Conclusions SSE combines sequence editor functions with analytical tools in a comprehensive and user-friendly package that assists considerably in bioinformatic and evolution research.

Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500–6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus–host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution.

Infectious diseases pose a major threat to safety of blood transfusion, organ and tissue and cell-based immunotherapies. Blood services worldwide perform very large-scale screening of blood donors for the major transfusion-transmissible infections (TTIs), HIV-1, hepatitis B and C viruses. However, ongoing and rapidly evolving threats to blood and transplant safety include the currently expanding number or arthropod-borne viruses, such as the current rapid northward expansion of West Nile, Chikungunya and Dengue viruses in Europe, and outbreaks of Oropouche and Zika viruses in Central and South America. The impact on blood and transplant safety of human virome components, including the large number of recently described and often highly prevalent human polyomaviruses, parvoviruses, papillomaviruses and anelloviruses, and human herpesviruses (HHVs) such as HHV-6 and − 7, remains poorly understood. Advances in genomics technologies, such as next-generation sequencing (NGS) provide the future opportunity to greatly expand the range of pathogens screened in donors, and to better monitor blood and transplant recipients for potential TTIs. A broader screening capability would enable blood banks to rapidly and effectively respond to new pandemic pathogens. However, the value of their future application for donor screening will require a much better understanding of the natural histories and potential disease associations of human virome components and other viruses incidentally detected on NGS screening. Furthermore, while genomic-based detection and ELISAs for pathogen-specific antibody can be readily applied for screening and excluding conventional pathogens, these are incapable of detecting and preventing transmission of proteinopathies, such as Creutzfeldt-Jakob disease (CJD) where the infectious agents possess no nucleic acid genome. The recent evidence for transmission of variant CJD in the UK through blood and plasma transfusion, and potential more extensive transfusion transmission of the amyloid disease, cerebral amyloid angiopathy, present potential existential threats to the ideal of complete blood safety if these findings are confirmed. A better understanding of the nature of “protein-only” transmissible agents in the aetiology of several forms of neurodegenerative disease is urgently required. Clinical trial number Not applicable.

Poliovirus is known to most people in the world as the cause of polio, a devastating paralytic disease from the past. Success in polio eradication has understandably translated into stricter containment plans for poliovirus, coordinated by WHO. In this Personal View, we discuss the impact of recent biosafety level 3+ guidelines for handling potential poliovirus-containing diagnostic specimens, which has resulted in closure of many national WHO poliovirus reference laboratories. This reduction in laboratory capacity has a knock-on effect of capability to detect and characterise non-polio enteroviruses in samples obtained from patients with neurological symptoms. The development is of concern given the widespread circulation of non-polio enteroviruses, their role as the most common cause of meningitis worldwide, and their involvement in other severe neurological conditions, such as acute flaccid myelitis and encephalitis. These disease presentations have increased substantially in the past decade, and have been associated with major outbreaks of enterovirus D68 and enterovirus A71, leaving many who survived with lasting paralysis and disabilities. To address this growing gap in diagnostic and surveillance capability, we have established the European Non-Poliovirus Enterovirus Network (also known as ENPEN) as a supra-national, non-commercial, core reference consortium. Our consortium will develop, test, and implement generic surveillance platforms for non-polio enteroviruses and other emerging viral diseases.

Background The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into families, genera and species and provides a regulated system for their nomenclature that is universally used in virus descriptions. Virus taxonomic assignments have traditionally been based upon virus phenotypic properties such as host range, virion morphology and replication mechanisms, particularly at family level. However, gene sequence comparisons provide a clearer guide to their evolutionary relationships and provide the only information that may guide the incorporation of viruses detected in environmental (metagenomic) studies that lack any phenotypic data. Results The current study sought to determine whether the existing virus taxonomy could be reproduced by examination of genetic relationships through the extraction of protein-coding gene signatures and genome organisational features. We found large-scale consistency between genetic relationships and taxonomic assignments for viruses of all genome configurations and genome sizes. The analysis pipeline that we have called ‘Genome Relationships Applied to Virus Taxonom y ’ (GRAViTy) was highly effective at reproducing the current assignments of viruses at family level as well as inter-family groupings into orders. Its ability to correctly differentiate assigned viruses from unassigned viruses, and classify them into the correct taxonomic group, was evaluated by threefold cross-validation technique. This predicted family membership of eukaryotic viruses with close to 100% accuracy and specificity potentially enabling the algorithm to predict assignments for the vast corpus of metagenomic sequences consistently with ICTV taxonomy rules. In an evaluation run of GRAViTy, over one half (460/921) of (near)-complete genome sequences from several large published metagenomic eukaryotic virus datasets were assigned to 127 novel family-level groupings. If corroborated by other analysis methods, these would potentially more than double the number of eukaryotic virus families in the ICTV taxonomy. Conclusions A rapid and objective means to explore metagenomic viral diversity and make informed recommendations for their assignments at each taxonomic layer is essential. GRAViTy provides one means to make rule-based assignments at family and order levels in a manner that preserves the integrity and underlying organisational principles of the current ICTV taxonomy framework. Such methods are increasingly required as the vast virosphere is explored.

The growth in global methane (CH₄) concentration, which had been ongoing since the industrial revolution, stalled around the year 2000 before resuming globally in 2007. We evaluate the role of the hydroxyl radical (OH), the major CH₄ sink, in the recent CH₄ growth. We also examine the influence of systematic uncertainties in OH concentrations on CH₄ emissions inferred from atmospheric observations. We use observations of 1,1,1-trichloroethane (CH₃CCl₃), which is lost primarily through reaction with OH, to estimate OH levels as well as CH₃CCl₃ emissions, which have uncertainty that previously limited the accuracy of OH estimates. We find a 64–70% probability that a decline in OH has contributed to the post-2007 methane rise. Our median solution suggests that CH₄ emissions increased relatively steadily during the late 1990s and early 2000s, after which growth was more modest. This solution obviates the need for a sudden statistically significant change in total CH₄ emissions around the year 2007 to explain the atmospheric observations and can explain some of the decline in the atmospheric 13CH₄/12CH₄ ratio and the recent growth in C₂H₆. Our approach indicates that significant OH-related uncertainties in the CH₄ budget remain, and we find that it is not possible to implicate, with a high degree of confidence, rapid global CH₄ emissions changes as the primary driver of recent trends when our inferred OH trends and these uncertainties are considered.

The rapid evolution of RNA viruses has been long considered to result from a combination of high copying error frequencies during RNA replication, short generation times and the consequent extensive fixation of neutral or adaptive changes over short periods. While both the identities and sites of mutations are typically modelled as being random, recent investigations of sequence diversity of SARS coronavirus 2 (SARS-CoV-2) have identified a preponderance of C->U transitions, proposed to be driven by an APOBEC-like RNA editing process. The current study investigated whether this phenomenon could be observed in datasets of other RNA viruses. Using a 5% divergence filter to infer directionality, 18 from 36 datasets of aligned coding region sequences from a diverse range of mammalian RNA viruses (including Picornaviridae , Flaviviridae , Matonaviridae , Caliciviridae and Coronaviridae ) showed a >2-fold base composition normalised excess of C->U transitions compared to U->C (range 2.1x–7.5x), with a consistently observed favoured 5’ U upstream context. The presence of genome scale RNA secondary structure (GORS) was the only other genomic or structural parameter significantly associated with C->U/U->C transition asymmetries by multivariable analysis (ANOVA), potentially reflecting RNA structure dependence of sites targeted for C->U mutations. Using the association index metric, C->U changes were specifically over-represented at phylogenetically uninformative sites, potentially paralleling extensive homoplasy of this transition reported in SARS-CoV-2. Although mechanisms remain to be functionally characterised, excess C->U substitutions accounted for 11–14% of standing sequence variability of structured viruses and may therefore represent a potent driver of their sequence diversification and longer-term evolution.

This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2022. The entire ICTV was invited to vote on 174 taxonomic proposals approved by the ICTV Executive Committee at its annual meeting in July 2021. All proposals were ratified by an absolute majority of the ICTV members. Of note, the Study Groups have started to implement the new rule for uniform virus species naming that became effective in 2021 and mandates the binomial ‘Genus_name species_epithet’ format with or without Latinization. As a result of this ratification, the names of 6,481 virus species (more than 60 percent of all species names currently recognized by ICTV) now follow this format.