Four principles to establish a universal virus taxonomy.

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., "arboviruses"), infecting a certain type of host (e.g., "mycoviruses," "bacteriophages") or displaying specific pathogenicity (e.g., "human immunodeficiency viruses"), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Virus taxonomy and the role of the International Committee on Taxonomy of Viruses (ICTV).

The taxonomy of viruses is developed and overseen by the International Committee on Taxonomy of Viruses (ICTV), which scrutinizes, approves and ratifies taxonomic proposals, and maintains a list of virus taxa with approved names (https://ictv.global). The ICTV has approximately 180 members who vote by simple majority. Taxon-specific Study Groups established by the ICTV have a combined membership of over 600 scientists from the wider virology community; they provide comprehensive expertise across the range of known viruses and are major contributors to the creation and evaluation of taxonomic proposals. Proposals can be submitted by anyone and will be considered by the ICTV irrespective of Study Group support. Thus, virus taxonomy is developed from within the virology community and realized by a democratic decision-making process. The ICTV upholds the distinction between a virus or replicating genetic element as a physical entity and the taxon category to which it is assigned. This is reflected by the nomenclature of the virus species taxon, which is now mandated by the ICTV to be in a binomial format (genus + species epithet) and is typographically distinct from the names of viruses. Classification of viruses below the rank of species (such as, genotypes or strains) is not within the remit of the ICTV. This article, authored by the ICTV Executive Committee, explains the principles of virus taxonomy and the organization, function, processes and resources of the ICTV, with the aim of encouraging greater understanding and interaction among the wider virology community.

Analysis of mutational history of multidrug-resistant genotypes with a mutagenetic tree model.

Human immunodeficiency virus (HIV) can develop resistance to all antiretroviral drugs. Multidrug resistance, however, is a rare event in modern HIV treatment, but can be life-threatening, particular in patients with very long therapy histories and in areas with limited access to novel drugs. To understand the evolution of multidrug resistance, we analyzed the EuResist database to uncover the accumulation of mutations over time. We hypothesize that the accumulation of resistance mutations is not acquired simultaneously and randomly across viral genotypes but rather tends to follow a predetermined order. The knowledge of this order might help to elucidate potential mechanisms of multidrug resistance. Our evolutionary model shows an almost monotonic increase of resistance with each acquired mutation, including less well-known nucleoside reverse transcriptase (RT) inhibitor-related mutations like K223Q, L228H, and Q242H. Mutations within the integrase (IN) (T97A, E138A/K G140S, Q148H, N155H) indicate high probability of multidrug resistance. Hence, these IN mutations also tend to be observed together with mutations in the protease (PR) and RT. We followed up with an analysis of the mutation-specific error rates of our model given the data. We identified several mutations with unusual rates (PR: M41L, L33F, IN: G140S). This could imply the existence of previously unknown virus variants in the viral quasispecies. In conclusion, our bioinformatics model supports the analysis and understanding of multidrug resistance.

Changes to virus taxonomy and the ICTV Statutes ratified by the International Committee on Taxonomy of Viruses (2023).

This article reports changes to virus taxonomy and taxon nomenclature that were approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2023. The entire ICTV membership was invited to vote on 174 taxonomic proposals that had been approved by the ICTV Executive Committee in July 2022, as well as a proposed revision of the ICTV Statutes. All proposals and the revised ICTV Statutes were approved by a majority of the voting membership. Of note, the ICTV continued the process of renaming existing species in accordance with the recently mandated binomial format and included gene transfer agents (GTAs) in the classification framework by classifying them as viriforms. In total, one class, seven orders, 31 families, 214 genera, and 858 species were created.

Differentiating between viruses and virus species by writing their names correctly.

Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.

Recent changes to virus taxonomy ratified by the International Committee on Taxonomy of Viruses (2022).

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.

Exploring the mechanisms behind HIV drug resistance in sub-Saharan Africa: conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights.

BACKGROUND: HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. METHODS: We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. RESULTS: Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and 'overarching'. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The 'adherence motivation' subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The 'healthcare burden' subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The 'ART overreliance' subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. CONCLUSIONS: Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.

Changes to virus taxonomy and to the International Code of Virus Classification and Nomenclature ratified by the International Committee on Taxonomy of Viruses (2021).

This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2021. The entire ICTV was invited to vote on 290 taxonomic proposals approved by the ICTV Executive Committee at its meeting in October 2020, as well as on the proposed revision of the International Code of Virus Classification and Nomenclature (ICVCN). All proposals and the revision were ratified by an absolute majority of the ICTV members. Of note, ICTV mandated a uniform rule for virus species naming, which will follow the binomial 'genus-species' format with or without Latinized species epithets. The Study Groups are requested to convert all previously established species names to the new format. ICTV has also abolished the notion of a type species, i.e., a species chosen to serve as a name-bearing type of a virus genus. The remit of ICTV has been clarified through an official definition of 'virus' and several other types of mobile genetic elements. The ICVCN and ICTV Statutes have been amended to reflect these changes.

Behavioral changes before lockdown and decreased retail and recreation mobility during lockdown contributed most to controlling COVID-19 in Western countries.

BACKGROUND: The COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus, hereby reducing the time-varying basic reproduction number (Rt) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a new peak in infections. In this study, we wanted to quantify the relative contribution of mobility restrictions, and that of behavioral changes that occurred already before the lockdowns, on the reduction of transmission during lockdowns in Western countries in early 2020. METHODS: Incidence data of cases and deaths from the first wave of infections for 35 Western countries (32 European, plus Israel, USA and Canada) were analyzed using epidemiological compartment models in a Bayesian framework. Mobility data was used to estimate the timing of changes associated with a lockdown, and was correlated with estimated reductions of Rt. RESULTS: Across all countries, the initial median estimate for Rt was 3.6 (95% IQR 2.4-5.2), and it was reduced to 0.78 (95% IQR 0.58-1.01) during lockdown. 48% (18-65%) of the reduction occurred already in the week before lockdown, with lockdown itself causing the remaining drop in transmission. A lower Rt during lockdown was independently associated with an increased time spent at home (0.21 per 10% more time, p < 0.007), and decreased mobility related to retail and recreation (0.07 per 10% less mobility, p < 0.008). CONCLUSIONS: In a Western population unaware of the risk, SARS-CoV-2 can be highly contagious with a reproduction number R0 > 5. Our results are consistent with evidence that recreational activities (including restaurant and bar visits) enable super-spreading events. Exiting from lockdown therefore requires continued physical distancing and tight control on this kind of activities.

A prospect on the use of antiviral drugs to control local outbreaks of COVID-19.

BACKGROUND: Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic. METHODS: Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process. RESULTS: For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out. CONCLUSION: In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.

Genome Detective: an automated system for virus identification from high-throughput sequencing data.

SUMMARY: Genome Detective is an easy to use web-based software application that assembles the genomes of viruses quickly and accurately. The application uses a novel alignment method that constructs genomes by reference-based linking of de novo contigs by combining amino-acids and nucleotide scores. The software was optimized using synthetic datasets to represent the great diversity of virus genomes. The application was then validated with next generation sequencing data of hundreds of viruses. User time is minimal and it is limited to the time required to upload the data. AVAILABILITY AND IMPLEMENTATION: Available online: http://www.genomedetective.com/app/typingtool/virus/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tracing the Impact of Public Health Interventions on HIV-1 Transmission in Portugal Using Molecular Epidemiology.

BACKGROUND: Estimation of temporal changes in human immunodeficiency virus (HIV) transmission patterns can help to elucidate the impact of preventive strategies and public health policies. METHODS: Portuguese HIV-1 subtype B and G pol genetic sequences were appended to global reference data sets to identify country-specific transmission clades. Bayesian birth-death models were used to estimate subtype-specific effective reproductive numbers (Re). Discrete trait analysis (DTA) was used to quantify mixing among transmission groups. RESULTS: We identified 5 subtype B Portuguese clades (26-79 sequences) and a large monophyletic subtype G Portuguese clade (236 sequences). We estimated that major shifts in HIV-1 transmission occurred around 1999 (95% Bayesian credible interval [BCI], 1998-2000) and 2000 (95% BCI, 1998-2001) for subtypes B and G, respectively. For subtype B, Re dropped from 1.91 (95% BCI, 1.73-2.09) to 0.62 (95% BCI,.52-.72). For subtype G, Re decreased from 1.49 (95% BCI, 1.39-1.59) to 0.72 (95% BCI, .63-.8). The DTA suggests that people who inject drugs (PWID) and heterosexuals were the source of most (>80%) virus lineage transitions for subtypes G and B, respectively. CONCLUSIONS: The estimated declines in Re coincide with the introduction of highly active antiretroviral therapy and the scale-up of harm reduction for PWID. Inferred transmission events across transmission groups emphasize the importance of prevention efforts for bridging populations.

PhyloGeoTool: interactively exploring large phylogenies in an epidemiological context.

MOTIVATION: Clinicians, health officials and researchers are interested in the epidemic spread of pathogens in both space and time to support the optimization of intervention measures and public health policies. Large sequence databases of virus sequences provide an interesting opportunity to study this spread through phylogenetic analysis. To infer knowledge from large phylogenetic trees, potentially encompassing tens of thousands of virus strains, an efficient method for data exploration is required. The clades that are visited during this exploration should be annotated with strain characteristics (e.g. transmission risk group, tropism, drug resistance profile) and their geographic context. RESULTS: PhyloGeoTool implements a visual method to explore large phylogenetic trees and to depict characteristics of strains and clades, including their geographic context, in an interactive way. PhyloGeoTool also provides the possibility to position new virus strains relative to the existing phylogenetic tree, allowing users to gain insight in the placement of such new strains without the need to perform a de novo reconstruction of the phylogeny. AVAILABILITY AND IMPLEMENTATION: https://github.com/rega-cev/phylogeotool (Freely available: open source software project). CONTACT: phylogeotool@kuleuven.be. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy.

BACKGROUND: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data. RESULTS: Our results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs. CONCLUSIONS: The patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies.

Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders.

BACKGROUND: Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed. STUDY DESIGN AND METHODS: This study includes all HIV-infected Dutch and Flemish donors in the period 2005 to 2014 (n = 55). Part of the HIV polymerase (pol) gene was amplified, sequenced, and compared with more than 10,000 HIV strains obtained from HIV-infected Dutch and Flemish patients. The most likely transmission route was determined based on HIV phylogeny and the donor's self-reported risk behavior during the exit interview. RESULTS: HIV-infected donors were predominantly male (69%), were repeat donors (73%), were born in the Netherlands or Belgium (95%), and harbored HIV Subtype B (68%). Seventy-five percent of HIV-infected male donors were part of robust phylogenetic clusters linked to male-to-male sex, while only 24% of HIV-infected male donors reported male-to-male sex during posttest counseling. Sex between men and women accounted for 13% of HIV infections in male donors and 93% of HIV infections in female donors based on phylogenetic analysis. Only 40% of HIV-infected female donors had HIV Subtype B; 65% of female donors reported a foreign partner and indeed HIV sequences interspersed with sequences from HIV-endemic areas abroad, in particular sub-Saharan Africa. CONCLUSION: HIV typing helps to understand HIV transmission routes in donor populations. We found substantial underreporting of male-to-male sex among HIV-infected male donors. Donor education on HIV risk factors and the danger of window-period donations and a donor environment that encourages frank disclosure of sexual behavior will contribute to a decrease of HIV-infected donors.

Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time.

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.