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1.
Nat Commun ; 11(1): 4620, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934242

RESUMO

Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.


Assuntos
Entamoeba/virologia , Giardia/virologia , Adulto , Estudos de Coortes , Fezes/parasitologia , Fezes/virologia , Feminino , Genoma Viral , Especificidade de Hospedeiro , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Fenômenos Fisiológicos Virais , Vírus/classificação , Vírus/genética , Adulto Jovem
2.
Biosens Bioelectron ; 166: 112436, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32750677

RESUMO

Our recent experience of the COVID-19 pandemic has highlighted the importance of easy-to-use, quick, cheap, sensitive and selective detection of virus pathogens for the efficient monitoring and treatment of virus diseases. Early detection of viruses provides essential information about possible efficient and targeted treatments, prolongs the therapeutic window and hence reduces morbidity. Graphene is a lightweight, chemically stable and conductive material that can be successfully utilized for the detection of various virus strains. The sensitivity and selectivity of graphene can be enhanced by its functionalization or combination with other materials. Introducing suitable functional groups and/or counterparts in the hybrid structure enables tuning of the optical and electrical properties, which is particularly attractive for rapid and easy-to-use virus detection. In this review, we cover all the different types of graphene-based sensors available for virus detection, including, e.g., photoluminescence and colorimetric sensors, and surface plasmon resonance biosensors. Various strategies of electrochemical detection of viruses based on, e.g., DNA hybridization or antigen-antibody interactions, are also discussed. We summarize the current state-of-the-art applications of graphene-based systems for sensing a variety of viruses, e.g., SARS-CoV-2, influenza, dengue fever, hepatitis C virus, HIV, rotavirus and Zika virus. General principles, mechanisms of action, advantages and drawbacks are presented to provide useful information for the further development and construction of advanced virus biosensors. We highlight that the unique and tunable physicochemical properties of graphene-based nanomaterials make them ideal candidates for engineering and miniaturization of biosensors.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Grafite , Pneumonia Viral/diagnóstico , Vírus/isolamento & purificação , Reações Antígeno-Anticorpo , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/tendências , Técnicas de Laboratório Clínico/instrumentação , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/estatística & dados numéricos , Colorimetria , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , DNA Viral/análise , DNA Viral/genética , Técnicas Eletroquímicas , Desenho de Equipamento , Grafite/química , Humanos , Luminescência , Nanoestruturas/química , Hibridização de Ácido Nucleico , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Pontos Quânticos/química , Análise Espectral Raman , Ressonância de Plasmônio de Superfície , Virologia/métodos , Vírus/genética , Vírus/patogenicidade
3.
Biosens Bioelectron ; 166: 112471, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777726

RESUMO

The infection and spread of pathogens (e.g., COVID-19) pose an enormous threat to the safety of human beings and animals all over the world. The rapid and accurate monitoring and determination of pathogens are of great significance to clinical diagnosis, food safety and environmental evaluation. In recent years, with the evolution of nanotechnology, nano-sized graphene and graphene derivatives have been frequently introduced into the construction of biosensors due to their unique physicochemical properties and biocompatibility. The combination of biomolecules with specific recognition capabilities and graphene materials provides a promising strategy to construct more stable and sensitive biosensors for the detection of pathogens. This review tracks the development of graphene biosensors for the detection of bacterial and viral pathogens, mainly including the preparation of graphene biosensors and their working mechanism. The challenges involved in this field have been discussed, and the perspective for further development has been put forward, aiming to promote the development of pathogens sensing and the contribution to epidemic prevention.


Assuntos
Bactérias/isolamento & purificação , Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Grafite , Pandemias , Pneumonia Viral/diagnóstico , Vírus/isolamento & purificação , Animais , Bactérias/genética , Bactérias/patogenicidade , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Grafite/química , Humanos , Técnicas de Diagnóstico Molecular , Nanotecnologia , Vírus/genética , Vírus/patogenicidade
4.
PLoS One ; 15(8): e0237780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845922

RESUMO

Modeling the behavior of zoonotic pandemic threats is a key component of their control. Many emerging zoonoses, such as SARS, Nipah, and Hendra, mutated from their wild type while circulating in an intermediate host population, usually a domestic species, to become more transmissible among humans, and this transmission route will only become more likely as agriculture and trade intensifies around the world. Passage through an intermediate host enables many otherwise rare diseases to become better adapted to humans, and so understanding this process with accurate mathematical models is necessary to prevent epidemics of emerging zoonoses, guide policy interventions in public health, and predict the behavior of an epidemic. In this paper, we account for a zoonotic disease mutating in an intermediate host by introducing a new mathematical model for disease transmission among three species. We present a model of these disease dynamics, including the equilibria of the system and the basic reproductive number of the pathogen, finding that in the presence of biologically realistic interspecies transmission parameters, a zoonotic disease with the capacity to mutate in an intermediate host population can establish itself in humans even if its R0 in humans is less than 1. This result and model can be used to predict the behavior of any zoonosis with an intermediate host and assist efforts to protect public health.


Assuntos
Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis Emergentes/epidemiologia , Reservatórios de Doenças/microbiologia , Modelos Biológicos , Zoonoses/epidemiologia , Animais , Animais Domésticos/microbiologia , Animais Selvagens/microbiologia , Bactérias/genética , Bactérias/patogenicidade , Doenças Transmissíveis Emergentes/microbiologia , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Surtos de Doenças/prevenção & controle , Vetores de Doenças , Especificidade de Hospedeiro/genética , Humanos , Taxa de Mutação , Vírus/genética , Vírus/patogenicidade , Zoonoses/microbiologia , Zoonoses/prevenção & controle , Zoonoses/transmissão
6.
Viruses ; 12(7)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674515

RESUMO

Next-generation sequencing (NGS) offers a powerful opportunity to identify low-abundance, intra-host viral sequence variants, yet the focus of many bioinformatic tools on consensus sequence construction has precluded a thorough analysis of intra-host diversity. To take full advantage of the resolution of NGS data, we developed HAplotype PHylodynamics PIPEline (HAPHPIPE), an open-source tool for the de novo and reference-based assembly of viral NGS data, with both consensus sequence assembly and a focus on the quantification of intra-host variation through haplotype reconstruction. We validate and compare the consensus sequence assembly methods of HAPHPIPE to those of two alternative software packages, HyDRA and Geneious, using simulated HIV and empirical HIV, HCV, and SARS-CoV-2 datasets. Our validation methods included read mapping, genetic distance, and genetic diversity metrics. In simulated NGS data, HAPHPIPE generated pol consensus sequences significantly closer to the true consensus sequence than those produced by HyDRA and Geneious and performed comparably to Geneious for HIV gp120 sequences. Furthermore, using empirical data from multiple viruses, we demonstrate that HAPHPIPE can analyze larger sequence datasets due to its greater computational speed. Therefore, we contend that HAPHPIPE provides a more user-friendly platform for users with and without bioinformatics experience to implement current best practices for viral NGS assembly than other currently available options.


Assuntos
Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Vírus/genética , Betacoronavirus/genética , Infecções por Coronavirus/virologia , Genoma Viral , Genômica/métodos , HIV/genética , Haplótipos , Hepacivirus/genética , Humanos , Pandemias , Pneumonia Viral/virologia
7.
Int J Mol Sci ; 21(14)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698494

RESUMO

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.


Assuntos
Neoplasias/prevenção & controle , RNA Viral/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Viroses/prevenção & controle , Animais , Vetores Genéticos/genética , Humanos , Camundongos , Neoplasias/virologia , Vacinação , Vírus/genética
8.
Scand J Immunol ; 92(3): e12928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32640050

RESUMO

Several enveloped viruses, particularly some RNA viruses, have high rates of mutation or replication, which can make them virulent pathogens in humans and other mammals. A proposed treatment could use synthesized proteins to mask pathogenic viral surface proteins to quickly induce an immune attack on specific enveloped viruses by using existing immune cells. One treatment could inject dual-protein ligand masks into patients' bloodstreams to mask pathogenic surface proteins used to infect mammalian cells. The mammalian immune system already uses an analogous, more complex structure called a pentraxin to neutralize some pathogens by connecting their surface proteins to immune cells. And several types of antiviral peptides have already experimentally demonstrated effectiveness in blocking various viral pathogen infections. These treatments offer advantages, especially for currently untreatable viral pathogens. Furthermore, using dual-protein ligands and the antigenic memory of some sub-populations of NK cells would also allow the creation of defacto vaccines based on a host's NK cells, instead of vaccines utilizing CD4 and CD8 α:ß T cells, which are limited by the requirement of MHC presentation of the target antigens to α:ß T cells. Targeted NK cell vaccines could attack host cells latently or actively infected by intracellular pathogens, even host cells having pathogen downregulated MHC antigen presentation. Eight postulates concerning the effects of pathogen mutation, or change in phenotype from genetic recombination or rearrangement, and replication rates on pathogen vs host dominance are also listed, which should be applicable to viral and non-viral pathogens.


Assuntos
Mutação , Viroses/virologia , Fenômenos Fisiológicos Virais , Replicação Viral , Vírus/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Taxa de Mutação , Fenótipo , Recombinação Genética , Viroses/tratamento farmacológico , Viroses/imunologia , Vírus/efeitos dos fármacos , Vírus/imunologia
9.
Arch Virol ; 165(9): 1935-1945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594322

RESUMO

Plants are a rich source of new antiviral, pharmacologically active agents. The naturally occurring plant alkaloid berberine (BBR) is one of the phytochemicals with a broad range of biological activity, including anticancer, anti-inflammatory and antiviral activity. BBR targets different steps in the viral life cycle and is thus a good candidate for use in novel antiviral drugs and therapies. It has been shown that BBR reduces virus replication and targets specific interactions between the virus and its host. BBR intercalates into DNA and inhibits DNA synthesis and reverse transcriptase activity. It inhibits replication of herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papillomavirus (HPV), and human immunodeficiency virus (HIV). This isoquinoline alkaloid has the ability to regulate the MEK-ERK, AMPK/mTOR, and NF-κB signaling pathways, which are necessary for viral replication. Furthermore, it has been reported that BBR supports the host immune response, thus leading to viral clearance. In this short review, we focus on the most recent studies on the antiviral properties of berberine and its derivatives, which might be promising agents to be considered in future studies in the fight against the current pandemic SARS-CoV-2, the virus that causes COVID-19.


Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Vírus/efeitos dos fármacos , Animais , Antivirais/química , Berberina/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Viroses/virologia , Replicação Viral/efeitos dos fármacos , Vírus/genética , Vírus/crescimento & desenvolvimento
10.
Forensic Sci Med Pathol ; 16(3): 457-462, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32578131

RESUMO

Death due to respiratory infection is commonly encountered at autopsy. With only one opportunity to obtain samples for identification of a causative agent, it is important to ensure that sampling regimes are optimized to provide the greatest detection, without the expense and redundancy that can arise from over-sampling. This study was performed retrospectively using data from Coronial autopsies over the period 2012-2019 from which swabs from the nasopharyngeal region, trachea and lung parenchyma, in addition to samples of lung tissue, had been submitted for multiplex PCR detection of respiratory pathogens. From 97 cases with all four samples, there were 24 with at least one positive result for viral infection. Some cases had multiple positive results and a total of 27 respiratory tract viruses were identified, of which rhinovirus, influenza A virus and respiratory syncytial virus were the most common. Seventeen of the 27 viral infections (63%) were identified in all four samples. However, in nearly all cases (96%) the nasopharyngeal swab detected the infective agent when the multiplex PCR panel had detected infection in any of the four sample types. A nasopharyngeal swab is considered to be an optimal sample for detection of respiratory tract viral infection. As the samples analyzed were acquired before the appearance of the COVID-19 virus, the applicability of this finding for COVID-19 screening is not established.


Assuntos
DNA Viral/isolamento & purificação , Pulmão/virologia , Reação em Cadeia da Polimerase Multiplex , Nasofaringe/virologia , Infecções Respiratórias/diagnóstico , Manejo de Espécimes , Virologia , Viroses/diagnóstico , Vírus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Causas de Morte , DNA Viral/classificação , DNA Viral/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Infecções Respiratórias/virologia , Estudos Retrospectivos , Viroses/virologia , Vírus/classificação , Vírus/genética
11.
Arch Virol ; 165(8): 1849-1853, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462285

RESUMO

To characterize their virome, double stranded RNAs extracted from scrapings of two Iranian grapevine varieties held in the Vassal-Montpellier Grapevine Biological Resources Center were analysed by high-throughput sequencing. In addition to several well-known grapevine viruses, divergent isolates of the newly described grapevine Kizil Sapak virus were identified in both accessions. Four complete genome sequences were determined, as well as two additional partial sequences (1,580 and 3,849 nucleotides long). These genomic sequences highlight the molecular diversity of this poorly known virus. In view of the absence of amplification of the GKSV isolates characterized here using the published primer pair, novel degenerate, polyvalent primers were designed, providing a more robust diagnosis.


Assuntos
Vírus/genética , Vitis/virologia , Vírus de DNA/genética , Genoma Viral/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Irã (Geográfico) , Fases de Leitura Aberta/genética , Filogenia , Doenças das Plantas/virologia , RNA de Cadeia Dupla/genética , Sequenciamento Completo do Genoma
12.
PLoS Comput Biol ; 16(5): e1007894, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453718

RESUMO

The rise in metagenomics has led to an exponential growth in virus discovery. However, the majority of these new virus sequences have no assigned host. Current machine learning approaches to predicting virus host interactions have a tendency to focus on nucleotide features, ignoring other representations of genomic information. Here we investigate the predictive potential of features generated from four different 'levels' of viral genome representation: nucleotide, amino acid, amino acid properties and protein domains. This more fully exploits the biological information present in the virus genomes. Over a hundred and eighty binary datasets for infecting versus non-infecting viruses at all taxonomic ranks of both eukaryote and prokaryote hosts were compiled. The viral genomes were converted into the four different levels of genome representation and twenty feature sets were generated by extracting k-mer compositions and predicted protein domains. We trained and tested Support Vector Machine, SVM, classifiers to compare the predictive capacity of each of these feature sets for each dataset. Our results show that all levels of genome representation are consistently predictive of host taxonomy and that prediction k-mer composition improves with increasing k-mer length for all k-mer based features. Using a phylogenetically aware holdout method, we demonstrate that the predictive feature sets contain signals reflecting both the evolutionary relationship between the viruses infecting related hosts, and host-mimicry. Our results demonstrate that incorporating a range of complementary features, generated purely from virus genome sequences, leads to improved accuracy for a range of virus host prediction tasks enabling computational assignment of host taxonomic information.


Assuntos
Biologia Computacional/métodos , Genoma Viral , Nucleotídeos/análise , Máquina de Vetores de Suporte , Algoritmos , Área Sob a Curva , Bactérias/virologia , Caudovirales/genética , Bases de Dados Factuais , Modelos Lineares , Metagenômica/métodos , Filogenia , Análise de Sequência de DNA , Vírus/genética
13.
Nat Commun ; 11(1): 2384, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404905

RESUMO

TATA-box binding protein (TBP) is required for every single transcription event in archaea and eukaryotes. It binds DNA and harbors two repeats with an internal structural symmetry that show sequence asymmetry. At various times in evolution, TBP has acquired multiple interaction partners and different organisms have evolved TBP paralogs with additional protein regions. Together, these observations raise questions of what molecular determinants (i.e. key residues) led to the ability of TBP to acquire new interactions, resulting in an increasingly complex transcriptional system in eukaryotes. We present a comprehensive study of the evolutionary history of TBP and its interaction partners across all domains of life, including viruses. Our analysis reveals the molecular determinants and suggests a unified and multi-stage evolutionary model for the functional innovations of TBP. These findings highlight how concerted chemical changes on a conserved structural scaffold allow for the emergence of complexity in a fundamental biological process.


Assuntos
Domínios Proteicos , TATA Box/genética , Proteína de Ligação a TATA-Box/genética , Transcrição Genética , Algoritmos , Sequência de Aminoácidos , Animais , Archaea/classificação , Archaea/genética , Archaea/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Sítios de Ligação/genética , Eucariotos/classificação , Eucariotos/genética , Eucariotos/metabolismo , Evolução Molecular , Humanos , Modelos Moleculares , Ligação Proteica , Homologia de Sequência de Aminoácidos , Proteína de Ligação a TATA-Box/química , Proteína de Ligação a TATA-Box/metabolismo , Vírus/classificação , Vírus/genética , Vírus/metabolismo
14.
Anal Chem ; 92(14): 9699-9705, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32441935

RESUMO

A novel coronavirus (SARS-CoV-2) was recently identified in patients with acute respiratory disease and spread quickly worldwide. A specific and rapid diagnostic method is important for early identification. The reverse-transcription recombinase-aided amplification (RT-RAA) assay is a rapid detection method for several pathogens. Assays were performed within 5-15 min as a one-step single tube reaction at 39 °C. In this study, we established two RT-RAA assays for the S and orf1ab gene of SARS-CoV-2 using clinical specimens for validation. The analytical sensitivity of the RT-RAA assay was 10 copies for the S and one copy for the orf1ab gene per reaction. Cross-reactions were not observed with any of the other respiratory pathogens. A 100% agreement between the RT-RAA and real-time PCR assays was accomplished after testing 120 respiratory specimens. These results demonstrate that the proposed RT-RAA assay will be beneficial as it is a faster, more sensitive, and more specific tool for the detection of SARS-CoV-2.


Assuntos
Betacoronavirus/química , Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase/métodos , Bactérias/química , Bactérias/genética , Reações Cruzadas , Sondas de DNA , Genes Virais , Humanos , Pandemias , Plasmídeos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Sensibilidade e Especificidade , Proteínas Virais/genética , Vírus/química , Vírus/genética
15.
Nature ; 581(7809): 470-474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32461640

RESUMO

The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders1-4. Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 109 per gram, and these numbers seem to persist throughout life5-7. We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections8-10. Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells; this second phase is modulated by breastfeeding.


Assuntos
Aleitamento Materno , Trato Gastrointestinal/virologia , Vírus/isolamento & purificação , Adulto , Bacteriólise , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Fezes/virologia , Feminino , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Humanos , Lactente , Recém-Nascido , Lisogenia , Masculino , Mecônio/virologia , Prófagos/genética , Prófagos/isolamento & purificação , Vírus/genética
16.
Nucleic Acids Res ; 48(W1): W366-W371, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32442274

RESUMO

Metagenomic sequencing combined with Oxford Nanopore Technology has the potential to become a point-of-care test for infectious disease in public health and clinical settings, providing rapid diagnosis of infection, guiding individual patient management and treatment strategies, and informing infection prevention and control practices. However, publicly available, streamlined, and reproducible pipelines for analyzing Nanopore metagenomic sequencing data are still lacking. Here we introduce NanoSPC, a scalable, portable and cloud compatible pipeline for analyzing Nanopore sequencing data. NanoSPC can identify potentially pathogenic viruses and bacteria simultaneously to provide comprehensive characterization of individual samples. The pipeline can also detect single nucleotide variants and assemble high quality complete consensus genome sequences, permitting high-resolution inference of transmission. We implement NanoSPC using Nextflow manager within Docker images to allow reproducibility and portability of the analysis. Moreover, we deploy NanoSPC to our scalable pathogen pipeline platform, enabling elastic computing for high throughput Nanopore data on HPC cluster as well as multiple cloud platforms, such as Google Cloud, Amazon Elastic Computing Cloud, Microsoft Azure and OpenStack. Users could either access our web interface (https://nanospc.mmmoxford.uk) to run cloud-based analysis, monitor process, and visualize results, as well as download Docker images and run command line to analyse data locally.


Assuntos
Genoma Viral , Metagenômica/métodos , Sequenciamento por Nanoporos/métodos , Software , Vírus/genética , Bactérias/genética , Bactérias/isolamento & purificação , Computação em Nuvem , Vírus/isolamento & purificação
17.
Int J Infect Dis ; 95: 133-141, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278934

RESUMO

BACKGROUND: Studies on the etiology of respiratory infections among children in Qatar and surrounding countries are limited. OBJECTIVES: To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. METHODS: We retrospectively collected and analyzed data of 33,404 children (<15 years) presented with influenza-like illness from 2012 to 2017. RESULTS: At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all cases, affecting 24%, 19.7%, and 18.5%, respectively. A prevalence of 5-10% was recorded for adenovirus, parainfluenza viruses (PIVs), human bocavirus (HboV), and human coronaviruses (HCoVs). Human metapneumovirus (HMPV), enteroviruses, M. pneumonia, and parechovirus had prevalences below 5%. While RSV, influenza, and HMPV exhibited strong seasonal activity in the winter, HRV was active during low RSV and influenza circulation. The burden of RSV exceeds that of influenza among young age groups, whereas influenza correlated positively with age. Further, HRV, adenovirus, influenza, and RSV infection rates varied significantly between male and females. CONCLUSION: This comprehensive multi-year study provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children.


Assuntos
Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Influenza Humana/virologia , Masculino , Orthomyxoviridae/isolamento & purificação , Prevalência , Catar/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/virologia , Estudos Retrospectivos , Rhinovirus/isolamento & purificação , Estações do Ano , Viroses/virologia , Vírus/genética , Vírus/isolamento & purificação
18.
Nat Microbiol ; 5(5): 668-674, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32341570

RESUMO

Virus taxonomy emerged as a discipline in the middle of the twentieth century. Traditionally, classification by virus taxonomists has been focussed on the grouping of relatively closely related viruses. However, during the past few years, the International Committee on Taxonomy of Viruses (ICTV) has recognized that the taxonomy it develops can be usefully extended to include the basal evolutionary relationships among distantly related viruses. Consequently, the ICTV has changed its Code to allow a 15-rank classification hierarchy that closely aligns with the Linnaean taxonomic system and may accommodate the entire spectrum of genetic divergence in the virosphere. The current taxonomies of three human pathogens, Ebola virus, severe acute respiratory syndrome coronavirus and herpes simplex virus 1 are used to illustrate the impact of the expanded rank structure. This new rank hierarchy of virus taxonomy will stimulate further research on virus origins and evolution, and vice versa, and could promote crosstalk with the taxonomies of cellular organisms.


Assuntos
Classificação , Vírus/classificação , Vírus/genética , Doenças Transmissíveis/virologia , Ebolavirus/classificação , Ecologia , Evolução Molecular , Genes Virais , Herpesvirus Humano 1/classificação , Humanos , Vírus da SARS/classificação
19.
PLoS One ; 15(4): e0227593, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294089

RESUMO

Genomic editing technologies are developing rapidly, promising significant developments for biomedicine, agriculture and other fields. In the present investigation, we analyzed and compared the process of innovation for six genomic technologies: viral vectors, RNAi, TALENs, meganucleases, ZFNs and CRISPR/Cas including the profile of the main research institutions and their funders, to understand how innovation evolved and what institutions influenced research trajectories. A Web of Science search of papers on viral vectors RNAi, CRISPR/Cas, TALENs, ZFNs and meganucleases was used to build a citation network of 16,746 papers. An analysis of network clustering combined with text mining was performed. For viral vectors, a long-term process of incremental innovation was identified, which was largely publicly funded in the United States and the European Union. The trajectory of RNAi research included clusters related to the study of RNAi as a biological phenomenon and its use in functional genomics, biomedicine and pest control. A British philanthropic organization and a US pharmaceutical company played a key role in the development of basic RNAi research and clinical application respectively, in addition to government and academic institutions. In the case of CRISPR/Cas research, basic science discoveries led to the technical improvements, and these two in turn provided the information required for the development of biomedical, agricultural, livestock and industrial applications. The trajectory of CRISPR/Cas research exhibits a geopolitical division of the investigation efforts between the US, as the main producer and funder of basic research and technical improvements, and Chinese research institutions increasingly leading applied research. Our results reflect a change in the model for financing science, with reduced public financing for basic science and applied research on publicly funded technological developments in the US, and the emergence of China as a scientific superpower, with implications for the development of applications of genomic technologies.


Assuntos
Pesquisa Biomédica/tendências , Tecnologia Biomédica/tendências , Organização do Financiamento/tendências , Edição de Genes/tendências , Invenções/tendências , Pesquisa Biomédica/economia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/organização & administração , Tecnologia Biomédica/economia , Tecnologia Biomédica/métodos , Tecnologia Biomédica/organização & administração , Sistemas CRISPR-Cas , China , Organização do Financiamento/economia , Organização do Financiamento/métodos , Edição de Genes/economia , Edição de Genes/métodos , Vetores Genéticos , Invenções/economia , Liderança , Política , Interferência de RNA , Estados Unidos , Vírus/genética
20.
Respir Res ; 21(1): 77, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228581

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking. METHODS: Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years. We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits. RESULTS: Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates. Virus infection was strongly associated with exacerbation events (P < 5E-20). Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation. Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event. Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung. CONCLUSIONS: This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations. It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications.


Assuntos
Bactérias/isolamento & purificação , Pulmão/microbiologia , Pulmão/virologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/virologia , Vírus/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Bactérias/genética , Carga Bacteriana , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Escarro/microbiologia , Escarro/virologia , Fatores de Tempo , Estados Unidos/epidemiologia , Carga Viral , Vírus/genética
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