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  • 机译 进化状态不明的孤儿病毒基因组揭示了感染植物的黄样病毒的独特谱系
    摘要:Advancements in high-throughput sequencing and associated bioinformatics methods have significantly expanded the RNA virus repertoire, including novel viruses with highly divergent genomes encoding “orphan” proteins that apparently lack homologous sequences. This absence of homologs in routine sequence similarity search complicates their taxonomic classification and raises a fundamental question: Do these orphan viral genomes represent bona ide viruses? In 2022, an orphan viral genome encoding a large polyprotein was identified in alfalfa (Medicago sativa) and thrips (Frankliniella occidentalis), and named Snake River alfalfa virus (SRAV). SRAV was initially proposed as an uncommon flavi-like virus identified in a plant host distantly related to family Flaviviridae. Subsequently, another research group showed its common occurrence in alfalfa but challenged its taxonomic position, suggesting it belongs to the family Endornaviridae. In this study, a large-scale analysis of 77 publicly available small RNA datasets indicates that SRAV could be detected across various tissues and cultivars of alfalfa, and has a broad geographical distribution. Moreover, profiles of the SRAV-derived small interfering RNAs (vsiRNAs) exhibited typical characteristics of viruses in plant hosts. The evolutionary analysis suggests that SRAV represents a unique class of plant-hosted flavi-like viruses with an unusual genome organization and evolutionary status, distinct from previously identified flavi-like viruses documented to infect plants. The latter shows a close evolutionary relationship to flavi-like viruses primarily found in plant-feeding invertebrates and lacks evidence of triggering host RNA interference (RNAi) responses so far. Moreover, mining the transcriptome shotgun assembly (TSA) database identified two novel viral sequences with a similar genome organization and evolutionary status to SRAV. In summary, our study resolves the disagreement regarding the taxonomic status of SRAV and suggests the potential existence of two distinct clades of plant-hosted flavi-like viruses with independent evolutionary origins. Furthermore, our research provides the first evidence of plant-hosted flavi-like viruses triggering the host’s RNAi antiviral response. The widespread occurrence of SRAV underscores its potential ecological significance in alfalfa, a crop of substantial economic importance.
  • 机译 基因组流行病学揭示了 SARS-CoV-2 在单一来源社区爆发中的变异和传播特性
    摘要:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic, which is still a global public health concern. During March 2022, a rapid and confined single-source outbreak of SARS-CoV-2 was identified in a community in Nanjing municipal city. Overall, 95 individuals had laboratory-confirmed SARS-CoV-2 infection. The whole genomes of 61 viral samples were obtained, which were all members of the BA.2.2 lineage and clearly demonstrated the presence of one large clade, and all the infections could be traced back to the original index case. The most distant sequence from the index case presented a difference of 4 SNPs, and 118 intrahost single-nucleotide variants (iSNVs) at 74 genomic sites were identified. Some minor iSNVs can be transmitted and subsequently rapidly fixed in the viral population. The minor iSNVs transmission resulted in at least two nucleotide substitutions among all seven SNPs identified in the outbreak, generating genetically diverse populations. We estimated the overall transmission bottleneck size to be 3 using 11 convincing donor–recipient transmission pairs. Our study provides new insights into genomic epidemiology and viral transmission, revealing how iSNVs become fixed in local clusters, followed by viral transmission across the community, which contributes to population diversity.
  • 机译 支持英国 SARS-CoV-2 基因组流行病学的系统发育和变异检出管道
    摘要:In response to the escalating SARS-CoV-2 pandemic, in March 2020 the COVID-19 Genomics UK (COG-UK) consortium was established to enable national-scale genomic surveillance in the UK. By the end of 2020, 49% of all SARS-CoV-2 genome sequences globally had been generated as part of the COG-UK programme, and to date, this system has generated >3 million SARS-CoV-2 genomes. Rapidly and reliably analysing this unprecedented number of genomes was an enormous challenge. To fulfil this need and to inform public health decision-making, we developed a centralized pipeline that performs quality control, alignment, and variant calling and provides the global phylogenetic context of sequences. We present this pipeline and describe how we tailored it as the pandemic progressed to scale with the increasing amounts of data and to provide the most relevant analyses on a daily basis.
  • 机译 对病毒使用物种和低于物种分类学术语的批评——是时候改变了?
    摘要:The International Committee for the Taxonomy of Viruses (ICTV) regulates assignment and names of virus species and higher taxa through its taxonomy proposal and ratification process. Despite using similar taxonomic ranks to those used elsewhere in biology, the ICTV has maintained the principle that species and other taxa are strictly categories with a formal nomenclature, whereas the viruses as objects are referenced through a parallel inventory of community-assigned virus names. This is strikingly different from common and scientific name synonyms for species used elsewhere in biology. The recent introduction of binomial names for virus species resembling biological scientific names has intensified this confusion in terms within the virology community and beyond. The ICTV taxonomy furthermore does not engage with or regulate classification below species and consequently lacks taxonomic terms or descriptions for important viral pathogens such as polioviruses, severe acute respiratory syndrome coronavirus type 2, HIV-1, and avian influenza as examples. The consequent reliance on community-adopted virus names, genotypes, and other categories often lacks clarity for clinical, biocontainment, and other regulatory purposes. This article proposes a revision of rules and procedures for species and below-species level classification. It recasts virus and virus species names as ‘common’ and ‘scientific’ names that are used in other biology nomenclature codes, each with expanded reference to both object and taxon. It further advocates the creation of a formal below-species taxonomic rank to define a new inventory of approved taxa and specified nomenclature below species. Adoption of the proposed changes will realign virus taxonomy with other biological nomenclatural codes and provide greater transparency and clarity in virology, medical, and regulatory fields.
  • 机译 降维提炼出季节性流感和 SARS-CoV-2 中复杂的进化关系
    摘要:Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis, multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS embeddings accurately represented pairwise genetic distances including the intermediate placement of recombinant SARS-CoV-2 lineages between parental lineages. Clusters from t-SNE embeddings accurately recapitulated known phylogenetic clades, H3N2 reassortment groups, and SARS-CoV-2 recombinant lineages. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.
  • 机译 偏远岛屿生态系统中病毒的多样性和跨物种传播:对野生动物保护的影响
    摘要:The ability of viruses to emerge in new species is influenced by aspects of host biology and ecology, with some taxa harbouring a high diversity and abundance of viruses. However, how these factors shape virus diversity at the ecosystem scale is often unclear. To better understand the pattern and determinants of viral diversity within an ecosystem, and to describe the novel avian viruses infecting an individual avian community, we performed a metagenomic snapshot of the virome from the entire avian community on remote Pukenui/Anchor Island in Aotearoa New Zealand. Through total RNA sequencing of 18 bird species, we identified 50 avian viruses from 9 viral families, of which 96% were novel. Of note, passerines (perching birds) exhibited high viral abundance and diversity, with viruses found across all nine viral families identified. We also identified numerous viruses infecting seabirds on the Island, including megriviruses, hepaciviruses, and hepatoviruses, while parrots exhibited an extremely low diversity of avian viruses. Within passerines, closely related astroviruses and hepatoviruses, and multiple identical hepe-like viruses, were shared among host species. Phylogenetic reconciliation analysis of these viral groups revealed a mixture of co-divergence and cross-species transmission, with virus host-jumping relatively frequent among passerines. In contrast, there was no evidence for recent cross-species virus transmission in parrots or seabirds. The novel pegiviruses and a flavivirus identified here also pose intriguing questions regarding their origins, pathogenicity, and potential impact on vertebrate hosts. Overall, these results highlight the importance of understudied remote island ecosystems as refugia for novel viruses, as well as the intricate interplay between host ecology and behaviour in shaping viral communities.
  • 机译 普瑞特韦与阿昔洛韦或膦甲酸联合使用可抑制 HSV-1 耐药性的演变
    摘要:The widespread use of antivirals in immunocompromised individuals has led to frequent occurrences of drug-resistant herpes simplex virus 1 (HSV-1) infections. Current antivirals target the viral DNA polymerase (DP), resulting in cross-resistance patterns that emphasize the need for novel treatment strategies. In this study, we assessed whether combining antivirals with different targets affects drug resistance emergence by passaging wild-type HSV-1 under increasing concentrations of acyclovir (ACV), foscarnet (phosphonoformic acid, PFA), or the helicase–primase inhibitor pritelivir (PTV), individually or in combination (ACV + PTV or PFA + PTV). The resistance selection procedure was initiated from two different drug concentrations for each condition. Deep sequencing and subsequent phenotyping showed the rapid acquisition of resistance mutations under monotherapy pressure, whereas combination therapy resulted in either no mutations or mutations conferring ACV and/or PFA resistance. Notably, mutations associated with PTV resistance were not detected after five passages under combination pressure. Strains resistant to both ACV and PTV were eventually obtained upon further passaging under ACV + PTV pressure initiated from lower drug concentrations. PFA + PTV dual treatment induced PFA resistance mutations in the DP, but PTV resistance mutations were not acquired, even after 15 passages. Our data suggest that combining the helicase–primase inhibitor PTV with a DP inhibitor may be an effective strategy to prevent drug resistance evolution in HSV-1.
  • 机译 关于评估拓扑收敛在贝叶斯系统发育推断中的重要性
    摘要:Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this reflection paper, we present two case studies—one on Ebola virus and one on HIV—illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Our results show the importance of running multiple replicate analyses and of carefully assessing topological convergence using the output of these replicate analyses. To this end, we illustrate different ways of assessing and visualizing the topological convergence of these replicates. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.
  • 机译 新出现的流行病中毒力的演变:从理论到实验进化再返回
    摘要:The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage λ spreading in continuous cultures of Escherichia coli. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis—including calculations of the selection gradients—and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage λ. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical, and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.
  • 机译 CovTransformer:用于 SARS-CoV-2 谱系频率预测的 transformer 模型
    摘要:With hundreds of SARS-CoV-2 lineages circulating in the global population, there is an ongoing need for predicting and forecasting lineage frequencies and thus identifying rapidly expanding lineages. Accurate prediction would allow for more focused experimental efforts to understand pathogenicity of future dominating lineages and characterize the extent of their immune escape. Here, we first show that the inherent noise and biases in lineage frequency data make a commonly-used regression-based approach unreliable. To address this weakness, we constructed a machine learning model for SARS-CoV-2 lineage frequency forecasting, called CovTransformer, based on the transformer architecture. We designed our model to navigate challenges such as a limited amount of data with high levels of noise and bias. We first trained and tested the model using data from the UK and the USA, and then tested the generalization ability of the model to many other countries and US states. Remarkably, the trained model makes accurate predictions two months into the future with high levels of accuracy both globally (in 31 countries with high levels of sequencing effort) and at the US-state level. Our model performed substantially better than a widely used forecasting tool, the multinomial regression model implemented in Nextstrain, demonstrating its utility in SARS-CoV-2 monitoring. Assuming a newly emerged lineage is identified and assigned, our test using retrospective data shows that our model is able to identify the dominating lineages 7 weeks in advance on average before they became dominant. Overall, our work demonstrates that transformer models represent a promising approach for SARS-CoV-2 forecasting and pandemic monitoring.
  • 机译 在大流行的第二年与不同人群免疫力相关的布朗克斯 COVID-19 住院人数的社区层面变异性
    摘要:The Bronx, New York, exhibited unique peaks in the number of coronavirus disease 2019 (COVID-19) cases and hospitalizations compared to national trends. To determine which features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus might underpin this local disease epidemiology, we conducted a comprehensive analysis of the genomic epidemiology of the four dominant strains of SARS-CoV-2 (Alpha, Iota, Delta, and Omicron) responsible for COVID-19 cases in the Bronx between March 2020 and January 2023. Genomic analysis revealed similar viral fitness for Alpha and Iota variants in the Bronx despite nationwide data showing higher cases of Alpha. However, Delta and Omicron variants had increased fitness within the borough. While the transmission dynamics of most variants in the Bronx corresponded with mutational fitness-based predictions of transmissibility, the Delta variant presented as an exception. Epidemiological modeling confirms Delta’s advantages of higher transmissibility in Manhattan and Queens, but not the Bronx; wastewater analysis suggests underdetection of cases in the Bronx. The Alpha variant had slightly faster growth but a lower carrying capacity compared to Iota and Delta in all four boroughs, suggesting stronger limitations on Alpha’s growth in New York City (NYC). The founder effect of Iota varied between higher vaccinated and lower vaccinated boroughs with longer delay, shorter duration, and lower fitness of the Alpha variant in lower vaccinated boroughs. Amino acid changes in T-cell and antibody epitopes revealed Delta and Iota having larger antigenic variability and antigenic profiles distant from local previously circulating lineages compared to Alpha. In concert with transmission modeling, our data suggest that the limited spread of Alpha may be due to a lack of adaptation to immunity in NYC. Overall, our study demonstrates that localized analyses and integration of orthogonal community-level datasets can provide key insights into the mechanisms of transmission and immunity patterns associated with regional COVID-19 incidence and disease severity that may be missed when analyzing broader datasets.
  • 机译 通过异种监测和病毒全基因组测序揭示澳大利亚东南部多种虫媒病毒的长期共循环
    摘要:Arbovirus surveillance of wild-caught mosquitoes is an affordable and sensitive means of monitoring virus transmission dynamics at various spatial-temporal scales, and emergence and re-emergence during epidemic and interepidemic periods. A variety of molecular diagnostics for arbovirus screening of mosquitoes (known as xeno-monitoring) are available, but most provide limited information about virus diversity. Polymerase chain reaction (PCR)-based screening coupled with RNA sequencing is an increasingly affordable and sensitive pipeline for integrating complete viral genome sequencing into surveillance programs. This enables large-scale, high-throughput arbovirus screening from diverse samples. We collected mosquitoes in CO2-baited light traps from five urban parks in Brisbane from March 2021 to May 2022. Mosquito pools of ≤200 specimens were screened for alphaviruses and flaviviruses using virus genus-specific primers and reverse transcription quantitative PCR (qRT-PCR). A subset of virus-positive samples was then processed using a mosquito-specific ribosomal RNA depletion method and then sequenced on the Illumina NextSeq. Overall, 54,670 mosquitoes representing 26 species were screened in 382 pools. Thirty detections of arboviruses were made in 28 pools. Twenty of these positive pools were further characterized using RNA sequencing generating 18 full-length genomes. These full-length sequences belonged to four medically relevant arboviruses: Barmah Forest, Ross River, Sindbis-like, and Stratford viruses. Phylogenetic and evolutionary analyses revealed the evolutionary progression of arbovirus lineages over the last 100 years, demonstrating that different epidemiological, immunological, and evolutionary processes may actively shape the evolution of Australian arboviruses. These results underscore the need for more genomic surveillance data to explore the complex evolutionary pressures acting on arboviruses. Overall, our findings highlight the effectiveness of our methodology, which can be applied broadly to enhance arbovirus surveillance in various ecological contexts and improve understanding of transmission dynamics.
  • 机译 关于疾病传播方式和大流行病的隐藏形式:Joshua Weitz 对无症状症的评论
    摘要:The importance of asymptomatic transmission was a key discovery in our efforts to study and intervene in the COVID-19 pandemic. In Asymptomatic (Johns Hopkins University Press, 2024), Joshua Weitz uses this aspect of SARS-CoV-2 natural history to discuss many counterintuitive characteristics of the pandemic. In this essay, I engage the arguments in the book, and discuss why asymptomatic transmission is such a critical dimension of the study of infectious diseases. I explore ideas contained within Asymptomatic and connect them to related issues in evolutionary virology and disease ecology, including epistemic uncertainty and the evolution of virulence. Furthermore, I comment on the broader messages in the text, including the gap between scientific knowledge and social understanding.
  • 机译 Kuafuorterviruses一种新型的逆转录病毒主要谱系
    摘要:Reverse-transcribing viruses (RTVs) characterized by reverse transcription required for their replication infect nearly all the eukaryotes. After decades of extensive analyses and discoveries, the understanding of the diversity of RTVs has largely stagnated. Herein, we discover a previously neglected lineage of RTVs, designated Kuafuorterviruses, in animals. Through screening over 8000 eukaryote genomes, we identify the presence of endogenous Kuafuorterviruses in the genomes of 169 eumetazoans dispersed across 11 animal phyla. Phylogenetic analyses and sequence similarity networks indicate that Kuafuorterviruses constitute a novel major lineage of RTVs. The discovery of Kuafuorterviruses refines our understanding of the diversity, evolution, and classification of RTVs and has implications in annotating animal genomes.
  • 机译 内源性病毒元件:洞察数据可用性和可访问性
    摘要:Endogenous viral elements (EVEs) are remnants of viral genetic material endogenized into the host genome. They have, in the last decades, attracted attention for their role as potential contributors to pathogenesis, drivers of selective advantage for the host, and genomic remnants of ancient viruses. EVEs have a nuanced and complex influence on both host health and evolution, and can offer insights on the deep evolutionary history of viruses. As an emerging field of research, several factors limit a comprehensive understanding of EVEs: they are currently underestimated and periodically overlooked in studies of the host genome, transcriptome, and virome. The absence of standardized guidelines for ensuring EVE-related data availability and accessibility following the FAIR (‘findable, accessible, interoperable, and reusable’) principles obstructs our ability to gather and connect information. Here, we discuss challenges to the availability and accessibility of EVE-related data and propose potential solutions. We identified the biological and research focus imbalance between different types of EVEs, and their overall biological complexity as genomic loci with viral ancestry, as potential challenges that can be addressed with the development of a user-oriented identification tool. In addition, reports of EVE identification are scattered between different subfields under different keywords, and EVE sequences and associated data are not properly gathered in databases. While developing an open and dedicated database might be ideal, targeted improvements of generalist databases might provide a pragmatic solution to EVE data and metadata accessibility. The implementation of these solutions, as well as the collective effort by the EVE scientific community in discussing and setting guidelines, is now drastically needed to lead the development of EVE research and offer insights into host–virus interactions and their evolutionary history.
  • 机译 中国家鹅 H6 流感病毒建立的进化特征:对宿主在生态系统中位置的影响
    摘要:Geese, both wild and domestic, are generally considered part of the natural reservoir for influenza A viruses. The highly pathogenic H5 Goose/Guangdong avian influenza virus lineage that is still causing outbreaks worldwide was first detected in domestic geese in 1996. However, while wild geese might have a somewhat restricted role in the influenza ecosystem, the role of domestic geese is little studied. Here, 109 H6 viruses isolated from domestic geese during 2001–2018 in southern China had their phylogeny, evolutionary dynamics, and molecular signatures characterized to examine the role of domestic geese. Our findings demonstrated that all geese H6 viruses were derived from H6 viruses established in ducks and that they subsequently formed three distinct hemagglutinin lineages. Rapid evolution of the hemagglutinin genes was not detected after the duck-to-goose transmissions of H6 viruses that then circulated in geese. Despite long-term persistence in geese, H6 viruses were rarely observed to transmit back to ducks or terrestrial poultry and never exchanged genes with viruses from other subtypes. Most geese H6 viruses maintained the primary molecular signatures of their duck precursors. This study raises the possibility that, rather than being part of the natural reservoir, domestic geese might be more like an aberrant host species for influenza A viruses, and perhaps a “dead-end” host.
  • 机译 肯尼亚沿海和内罗毕注射吸毒者中 HIV-1 传播趋势的系统发育评估
    摘要:Although recent modeling suggests that needle–syringe programs (NSPs) have reduced parenteral HIV transmission among people who inject drugs (PWID) in Kenya, the prevalence in this population remains high (∼14–20%, compared to ∼4% in the larger population). Reducing transmission or acquisition requires understanding historic and modern transmission trends, but the relationship between the PWID HIV-1 sub-epidemic and the general epidemic in Kenya is not well understood. We incorporated 303 new (2018–21) HIV-1 pol sequences from PWID and their sexual and injecting partners with 2666 previously published Kenyan HIV-1 sequences to quantify relative rates and direction of HIV-1 transmissions involving PWID from the coast and Nairobi regions of Kenya. We used genetic similarity cluster analysis (thresholds: patristic distance <0.045 and <0.015) and maximum likelihood and Bayesian ancestral state reconstruction to estimate transmission histories at the population group (female sex workers, men who have sex with men, PWID, or general population) and regional (coast or Nairobi) levels. Of 1081 participants living with HIV-1, 274 (25%) were not virally suppressed and 303 (28%) had sequences available. Of new sequences from PWID, 58% were in phylogenetic clusters at distance threshold <0.045. Only 21% of clusters containing sequences from PWID included a second PWID sequence. Sequences from PWID were similarly likely to cluster with sequences from female sex workers, men who have sex with men, and the general population. Ancestral state reconstruction suggested that transmission to PWID from other populations was more common than from PWID to other populations. This study expands our understanding of the HIV-1 sub-epidemic among PWID in Kenya by incorporating four times more HIV-1 sequences from this population than prior studies. Despite recruiting many PWID from local sexual and injecting networks, we found low levels of linked transmission in this population. This may suggest lower relative levels of parenteral transmission in recent years and supports maintaining NSPs among PWID, while also strengthening interventions to reduce HIV-1 sexual acquisition and transmission for this population.
  • 机译 一种分析超突变 HIV 前病毒的简单系统发育方法揭示了它们在抗逆转录病毒治疗过程中的动态和持久性
    摘要:Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV env-gp120 sequences isolated from six women over a median of 18 years of follow-up—including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART—we evaluated three approaches for masking hypermutation in nucleotide alignments. Our goals were to (i) reconstruct phylogenies that can be used for molecular dating and (ii) phylogenetically infer the integration dates of hypermutated proviruses persisting during ART. Two of the approaches (stripping all positions containing putative APOBEC3 mutations from the alignment or replacing individual putative APOBEC3 mutations in hypermutated sequences with the ambiguous base R) consistently normalized tree topologies, eliminated erroneous clustering of hypermutated proviruses, and brought env-intact and hypermutated proviruses into comparable ranges with respect to multiple tree-based metrics. Importantly, these corrected trees produced integration date estimates for env-intact proviruses that were highly concordant with those from benchmark trees that excluded hypermutated sequences, supporting the use of these corrected trees for molecular dating. Subsequent molecular dating of hypermutated proviruses revealed that these sequences spanned a wide within-host age range, with the oldest ones dating to shortly after infection. This indicates that hypermutated proviruses, like other provirus types, begin to be seeded into the proviral pool immediately following infection and can persist for decades. In two of the six participants, hypermutated proviruses differed from env-intact ones in terms of their age distributions, suggesting that different provirus types decay at heterogeneous rates in some hosts. These simple approaches to reconstruct hypermutated provirus’ evolutionary histories reveal insights into their in vivo origins and longevity toward a more comprehensive understanding of HIV persistence during ART.
  • 机译 揭示鱼酸心肌炎病毒的基因组景观:大西洋鲑的突变频率、病毒多样性和进化动力学
    摘要:Over a decade since its discovery, piscine myocarditis virus (PMCV) remains a significant pathogen in Atlantic salmon aquaculture. Despite this significant impact, the genomic landscape, evolutionary dynamics, and virulence factors of PMCV are poorly understood. This study enhances the existing PMCV sequence dataset by adding 34 genome sequences and 202 new ORF3 sequences from clinical cardiomyopathy syndrome (CMS) cases in Norwegian aquaculture. Phylogenetic analyses, also including sequences from the Faroe Islands and Ireland revealed that PMCV sequences are highly conserved with distinct clustering by country of origin. Still, single CMS outbreaks display multiple PMCV variants, and although some clustering was seen by case origin, occasional grouping of sequences from different cases was also apparent. Temporal data from selected cases indicated increased sequence diversity in the population. We hypothesize that multiple bottlenecks and changing infection dynamics in the host population, with transfer to naïve individuals over time, represent a continuous selection pressure on the virus populations. No clear relation was found between PMCV variants and the severity of heart pathology. However, specific non-synonymous and synonymous mutations that might impact protein function and gene expression efficiency were identified. An additional factor that may impact PMCV replication is the presence of defective viral genomes, a novel finding for viruses of the order Ghabrivirales. This study provides new insights into PMCV genomic characteristics and evolutionary dynamics, highlighting the complex interplay of genetic diversity, virulence markers, and host-pathogen interactions, underscoring the epidemiological complexity of the virus.Keywords: piscine myocarditis virus; evolutionary dynamics; diversity; phylogeny; genomic sequencing; defective viral genomes
  • 机译 新型欧亚起源的 H5Nx 禽流感病毒在加拿大大西洋地区的反复侵袭和传播
    摘要:Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards. This lineage has evolved and diversified over time, with a recent important derivative being the 2.3.4.4b sub-lineage, which has caused significant mortality events in wild bird populations. An H5N1 clade 2.3.4.4b virus was transmitted into North America from Eurasia in 2021, with the first detection being in Newfoundland and Labrador in Atlantic Canada, and this virus and its reassortants then spread broadly throughout North America and beyond. Following the first 2021 detection, there have been three additional known incursions of Eurasian-origin strains into Atlantic Canada, a second H5N1 strain in 2022 and two H5N5 strains in 2023. In this study, we document a fifth incursion in Atlantic Canada that occurred in 2023 by another H5N5 strain. This strain spread throughout Atlantic Canada and into Quebec, infecting numerous species of wild birds and mammals. Genomic analysis revealed mammalian-adaptive mutations in some of the detected viruses (PB2-E627K and PB2-D701N) and mutations in the hemagglutinin (HA) and neuraminidase (NA) genes that are associated with enhanced viral fitness and avian transmission capabilities. Our findings indicate that this virus is continuing to circulate in wildlife, and confirms Atlantic Canada is an important North American entry point for Eurasian IAVs. Continued surveillance and genomic analysis of IAVs detected in the region is crucial to monitor the evolution of these viruses and assess potential risks to wildlife and public health.

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