Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 16.666
Filtrar
2.
Infectio ; 25(4): 296-299, oct.-dic. 2021. tab, graf
Artículo en Español | LILACS, COLNAL | ID: biblio-1286726

RESUMEN

Resumen La identificación del nuevo Coronavirus tipo 2 en marzo de 2020 en Colombia ha generado paradigmas e incógnitas en la epidemiología nacional con respecto a la llegada aproximada del virus y sus mecanismos de diseminación local en los departamentos y ciudades principales. Presentamos el caso de un paciente con COVID-19 que tuvo su inicio de síntomas dos semanas antes de la declaración del primer caso en Colombia, lo que sugiere circulación del virus y transmisión local en Colombia previo a la declaración de la epidemia.


Abstract The identification of Coronavirus type 2 in March 2020 in Colombia has generated paradigms and unknows in the national epidemiology regarding the approxi mate arrival of the virus and its mechanisms of local dissemination in the main departments and cities. We present the case of a patient with COVID-19 that had its onset of symptoms two weeks before the declaration of the first case in Colombia, wich moves the circulation of the virus and local transmission in Colombia prior the declaration of the epidemic.


Asunto(s)
Humanos , Masculino , Adulto , Coronavirus , COVID-19 , Neumonía , Virus , Epidemiología , Colombia , Epidemias , Infecciones
3.
Infectio ; 25(4): 289-292, oct.-dic. 2021. tab, graf
Artículo en Español | LILACS, COLNAL | ID: biblio-1286724

RESUMEN

Resumen La trombosis de senos venosos cerebrales es un evento infrecuente en la población pediátrica y sus manifestaciones clínicas pueden variar dependiendo de la localización y extensión de la lesión, etiología o grupo etario (1); así mismo, la asociación de esta patología con virus es poco común, sin embargo, se han repor tado casos de trombosis de senos venosos en pacientes adultos con SARS-CoV-2 en relación con los mecanismos de lesión endotelial y respuesta inflamatoria que desencadena mecanismos procoagulantes. A continuación se presenta el primer caso reportado en Colombia de un caso de trombosis venosa cerebral en un lactante previamente sano, que debuta con un cuadro infeccioso gastrointestinal que resuelve y una semana después se presenta con cefalea y paralisis del VI par craneal derecho. Se documentó por angioto mografía trombosis del seno venoso sagital con extensión a senos transversos; los laboratorios fueron negativos para otras causas sistémicas y con prueba de anticuerpos para coronavirus positiva.


Abstract Cerebral venous sinus thrombosis is infrequent in the pediatric population and its clinical manifestations may vary depending on the anatomical location and the extent of the lesion, etiology or age group(1). The association of this pathology with viruses is uncommon, however, cases in adults with SARS-Cov2 have been reported triggered by procoagulant mechanisms due to endothelial injury and inflammatory response. The following article is the first reported case in Colombia of cerebral venous thrombosis in a previously healthy child, who debuted with gastrointestinal infectious disease and a week later with headache and sixth right cranial nerve palsy . The diagnosis of sagittal venous sinus thrombosis with extension to transverse sinuses was documented in a computed tomography angiography; laboratories for systemic diseases were negative and antibodies for coronavirus were positive.


Asunto(s)
Humanos , Masculino , Lactante , Trombosis de los Senos Intracraneales , SARS-CoV-2 , COVID-19 , Trombosis , Virus , Coronavirus , Trombosis de la Vena , Enfermedades de los Nervios Craneales , Senos Transversos , Cefalea
4.
Infectio ; 25(4): 270-275, oct.-dic. 2021. tab, graf
Artículo en Español | LILACS, COLNAL | ID: biblio-1286721

RESUMEN

Resumen Objetivo: Comparar la expresión de mRNA y proteínas de SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 y HAND1 en pacientes con lesión intra-epitelial cervical de bajo y alto grado, con posterior progresión o regresión. Material y Método: Se realizó análisis de expresión de genes mediante RT-PCR y análisis de expresión de proteínas por inmunohistoquímica. El análisis estadís tico fue realizado con las pruebas: Wilcoxon, coeficiente de correlación de Spearman e índice de concordancia. Las muestras fueron pareadas en momento 1 y momento 2. Resultados: SFRP1 mostró tendencia de mayor expresión de mRNA en lesión intra-epitelial de bajo grado (momento 2) Vs. alto grado (momento 1). La expresión de proteínas por inmunohistoquímica de SFRP1 en casos de progresión (83,3 %) mostró disminución en su graduación (p = 0,0313*); los demás genes en estudio no tuvieron cambios estadísticamente significativos. Discusión: SFRP1 mostró comportamiento ajustado a resultados de estudios previos donde se encontró hipermetilado en lesiones intra-epiteliales de alto grado; su subexpresión por hipermetilación se reportó en otros canceres, proceso que colabora con su silenciamiento y transición epitelial-mesenquimatosa del cáncer de cuello uterino. Conclusiones. SFRP1 es potencial biomarcador en lesiones preneoplásicas del cuello uterino asociadas al virus de papiloma humano.


Abstract Objective. The aim of this work was to compare the expression of mRNA and proteins of SFRP1, PTPRN, CDO1, EDNRB, CDX2, EPB41L3 and HAND1 in patients with low and high grade cervical intraepithelial lesion, with subsequent progression or regression. Material and Methods: Gene expression analysis was conducted through RT-PCR and protein expression analysis was performed by immunohistochemistry. The statistics analysis were Wilcoxon test, Spearman's correlation coefficient and concordance index. The samples were paired during moment 1 (initial patient diag nosis) and moment 2 (follow-up histological diagnosis). Results: SFRP1 showed a trend of higher mRNA expression in low-grade intra-epithelial lesions (moment 2) Vs. high-grade (moment 1). The expression of proteins by immunohistochemistry of SFRP1 in progression cases (83.3%) showed a decrease in its graduation (p = 0.0313*); the other genes under study had no statistically significant. Discussion: SFRP1 showed a biological behavior adjusted to the results of previous studies where hypermethylation was found in high-grade intra-epithelial lesions; its subexpression by hypermethylation has been reported in other cancers, a process that collaborates with its silencing and epithelial-mesenchymal tran sition of cervical. Conclusions. SFRP1 is a potential biomarker in preneoplastic lesions of the cervix associated with human papillomavirus.


Asunto(s)
Humanos , Femenino , Adulto , Papiloma , Sondas de ADN de HPV , Virus , Proteínas , Neoplasias del Cuello Uterino , Progresión de la Enfermedad , Alphapapillomavirus
5.
Sci Rep ; 11(1): 19579, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599242

RESUMEN

The increasing risk from viral outbreaks such as the ongoing COVID-19 pandemic exacerbates the need for rapid, affordable and sensitive methods for virus detection, identification and quantification; however, existing methods for detecting virus particles in biological samples usually depend on multistep protocols that take considerable time to yield a result. Here, we introduce a rapid fluorescence in situ hybridization (FISH) protocol capable of detecting influenza virus, avian infectious bronchitis virus and SARS-CoV-2 specifically and quantitatively in approximately 20 min, in virus cultures, combined nasal and throat swabs with added virus and likely patient samples without previous purification. This fast and facile workflow can be adapted both as a lab technique and a future diagnostic tool in enveloped viruses with an accessible genome.


Asunto(s)
Hibridación Fluorescente in Situ/métodos , ARN Viral/aislamiento & purificación , Virus/aislamiento & purificación , Virus/genética
6.
BMJ Open ; 11(10): e052473, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34620665

RESUMEN

PURPOSE: We describe here a multicentric community-dwelling cohort of older adults (>60 years of age) established to estimate incidence, study risk factors, healthcare utilisation and economic burden associated with influenza and respiratory syncytial virus (RSV) in India. PARTICIPANTS: The four sites of this cohort are in northern (Ballabgarh), southern (Chennai), eastern (Kolkata) and western (Pune) parts of India. We enrolled 5336 participants across 4220 households and began surveillance in July 2018 for viral respiratory infections with additional participants enrolled annually. Trained field workers collected data about individual-level and household-level risk factors at enrolment and quarterly assessed frailty and grip strength. Trained nurses surveilled weekly to identify acute respiratory infections (ARI) and clinically assessed individuals to diagnose acute lower respiratory infection (ALRI) as per protocol. Nasal and oropharyngeal swabs are collected from all ALRI cases and one-fifth of the other ARI cases for laboratory testing. Cost data of the episode are collected using the WHO approach for estimating the economic burden of seasonal influenza. Handheld tablets with Open Data Kit platform were used for data collection. FINDINGS TO DATE: The attrition of 352 participants due to migration and deaths was offset by enrolling 680 new entrants in the second year. All four sites reported negligible influenza vaccination uptake (0.1%-0.4%), low health insurance coverage (0.4%-22%) and high tobacco use (19%-52%). Ballabgarh had the highest proportion (54.4%) of households in the richest wealth quintile, but reported high solid fuel use (92%). Frailty levels were highest in Kolkata (11.3%) and lowest in Pune (6.8%). The Chennai cohort had highest self-reported morbidity (90.1%). FUTURE PLANS: The findings of this cohort will be used to inform prioritisation of strategies for influenza and RSV control for older adults in India. We also plan to conduct epidemiological studies of SARS-CoV-2 using this platform.


Asunto(s)
COVID-19 , Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Virus , Anciano , Humanos , India/epidemiología , Lactante , Gripe Humana/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2
7.
J Water Health ; 19(5): 775-784, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34665770

RESUMEN

The detection of SARS-CoV in wastewater has been proposed as a tool for monitoring COVID-19 at the community level. Although many reports have been published about detecting viral RNA in wastewater and its presence has been linked to infected people, appropriate analytical methodologies to use this approach have not yet been established. In this study, we compared ultrafiltration, polyethylene glycol precipitation, flocculation using AlCl3, and flocculation with skim milk for the recovery of SARS-CoV-2, using RNA from patients with positive diagnoses for COVID-19 and Pseudomonas phage φ6 as the control. We also evaluated the primers for detecting the E, RdRp, and N genes of the virus, as well as different storage times. Differences in the recovery efficiencies were evident with the different concentration methods, the best being ultrafiltration and precipitation with aluminum, which had recovery rates of 42.0% and 30.0%, respectively, when virus was present at high levels. Significant differences were found between the recoveries using wastewater and deionized water and between different storage times, with better recoveries for 6 and 12 h samplings. The E gene was the only one detected in all the samples analyzed. The results show that although this approach can provide important data for studying the pandemic, clear protocols are necessary for investigations to be comparable.


Asunto(s)
COVID-19 , Virus , Humanos , Pandemias , SARS-CoV-2 , Aguas Residuales
8.
Front Cell Infect Microbiol ; 11: 725043, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34595133

RESUMEN

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.


Asunto(s)
Virosis , Virus , Ciclo del Ácido Cítrico , Humanos , Inflamación , Replicación Viral
9.
Philos Trans R Soc Lond B Biol Sci ; 376(1837): 20200358, 2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34538140

RESUMEN

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.


Asunto(s)
Reservorios de Enfermedades/virología , Salud Global , Pandemias/prevención & control , Zoonosis/prevención & control , Zoonosis/virología , Animales , Animales Salvajes , COVID-19/prevención & control , COVID-19/veterinaria , Ecología , Humanos , Laboratorios , Aprendizaje Automático , Factores de Riesgo , SARS-CoV-2 , Virus , Zoonosis/epidemiología
10.
Cells ; 10(9)2021 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34571822

RESUMEN

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.


Asunto(s)
Esfingolípidos/metabolismo , Virosis , Transporte Biológico , Membrana Celular/química , Ceramidas/metabolismo , Sistemas de Liberación de Medicamentos , VIH/crecimiento & desarrollo , Interacciones Microbiota-Huesped , Membranas Intracelulares/química , SARS-CoV-2/crecimiento & desarrollo , Virión , Replicación Viral , Virus/crecimiento & desarrollo
11.
Biocontrol Sci ; 26(3): 177-180, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34556620

RESUMEN

Ethanol is an effective disinfectant against the novel coronavirus SARS-CoV-2. However, its effective concentration has not been shown, and we therefore analyzed the effects of different concentrations of ethanol on SARS-CoV-2. When SARS-CoV-2 was treated with varying ethanol concentrations and examined for changes in infectivity, the ethanol concentration at which 99% of the infectious titers were reduced was 24.1% (w/w) [29.3% (v/v)]. For reference, ethanol susceptibility was also examined with other envelope viruses, including influenza virus, vesicular stomatitis virus in the family Rhabdoviridae, and Newcastle disease virus in the family Paramyxoviridae, and the 99% inhibitory concentrations were found to be 28.8%(w/w) [34.8% (v/v)], 24.0% (w/w) [29.2% (v/v)], and 13.3% (w/w) [16.4% (v/v)], respectively. Some differences from SARS-CoV-2 were observed, but the differences were not significant. It was concluded that ethanol at a concentration of 30%(w/w) [36.2% (v/v)] almost completely inactivates SARS-CoV-2.


Asunto(s)
Desinfectantes/farmacología , Etanol/farmacología , SARS-CoV-2/efectos de los fármacos , COVID-19/virología , Desinfectantes/análisis , Etanol/análisis , Humanos , SARS-CoV-2/crecimiento & desarrollo , SARS-CoV-2/fisiología , Inactivación de Virus/efectos de los fármacos , Virus/efectos de los fármacos , Virus/crecimiento & desarrollo
12.
Commun Biol ; 4(1): 1086, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34526645

Asunto(s)
Virus , Membrana Celular
13.
Front Cell Infect Microbiol ; 11: 590989, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34513721

RESUMEN

Clustered regularly interspaced short palindromic repeats (CRISPR) systems are a set of versatile gene-editing toolkit that perform diverse revolutionary functions in various fields of application such as agricultural practices, food industry, biotechnology, biomedicine, and clinical research. Specially, as a novel antiviral method of choice, CRISPR/Cas9 system has been extensively and effectively exploited to fight against human infectious viruses. Infectious diseases including human immunodeficiency virus (HIV), hepatitis B virus (HBV), human papillomavirus (HPV), and other viruses are still global threats with persistent potential to probably cause pandemics. To facilitate virus removals, the CRISPR/Cas9 system has already been customized to confer new antiviral capabilities into host animals either by modifying host genome or by directly targeting viral inherent factors in the form of DNA. Although several limitations and difficulties still need to be conquered, this technology holds great promises in the treatment of human viral infectious diseases. In this review, we will first present a brief biological feature of CRISPR/Cas9 systems, which includes a description of CRISPR/Cas9 structure and composition; thereafter, we will focus on the investigations and applications that employ CRISPR/Cas9 system to combat several human infectious viruses and discuss challenges and future perspectives of using this new platform in the preclinical and clinical settings as an antiviral strategy.


Asunto(s)
Enfermedades Transmisibles , Virosis , Virus , Animales , Sistemas CRISPR-Cas , Virus de la Hepatitis B/genética , Humanos , Virosis/genética , Virus/genética
14.
Nat Commun ; 12(1): 5398, 2021 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-34518545

RESUMEN

As one of the largest biotechnological applications, activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses, with 10-1,000-fold higher concentrations than in natural environments. However, the compositional variation and host-connections of AS viruses remain poorly explored. Here, we report a catalogue of ~50,000 prokaryotic viruses from six WWTPs, increasing the number of described viral species of AS by 23-fold, and showing the very high viral diversity which is largely unknown (98.4-99.6% of total viral contigs). Most viral genera are represented in more than one AS system with 53 identified across all. Viral infection widely spans 8 archaeal and 58 bacterial phyla, linking viruses with aerobic/anaerobic heterotrophs, and other functional microorganisms controlling nitrogen/phosphorous removal. Notably, Mycobacterium, notorious for causing AS foaming, is associated with 402 viral genera. Our findings expand the current AS virus catalogue and provide reference for the phage treatment to control undesired microorganisms in WWTPs.


Asunto(s)
Ciclo del Carbono , Células Procariotas/virología , Aguas del Alcantarillado/virología , Viroma/genética , Virus/genética , Purificación del Agua/métodos , Archaea/clasificación , Archaea/genética , Archaea/virología , Bacterias/clasificación , Bacterias/genética , Bacterias/virología , Metabolismo Energético/genética , Genes Virales/genética , Variación Genética , Interacciones Huésped-Patógeno , Sistemas de Lectura Abierta/genética , Células Procariotas/metabolismo , Análisis de Secuencia de ADN/métodos , Aguas del Alcantarillado/microbiología , Virus/clasificación , Virus/metabolismo
15.
Front Cell Infect Microbiol ; 11: 694020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34527601

RESUMEN

Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.


Asunto(s)
Arbovirus , Culicidae , Virus de Insectos , Virus , Animales , Femenino , Humanos , Metagenómica
16.
Anal Chem ; 93(38): 12938-12943, 2021 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-34520175

RESUMEN

We use the Φ6 bacteriophage previously exploited as a BSL-1 surrogate of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS) coronavirus to obtain the first high-resolution gas phase mobility spectra of an enveloped virus. The relative full width at half-maximum found for the viral mobility distribution (FWHMZ < 3.7%) is substantially narrower than that reported by prior mobility or microscopy studies with other enveloped viruses. It is nevertheless not as narrow as that recently found for several non-enveloped viruses (FWHMZ ≈ 2%), presumably due to particle to particle variability of enveloped viruses. This 3.7% is an upper bound to the actual width. Nevertheless, the well-defined mobility peaks obtained indicate that gas phase mobility analysis is a more discriminating methodology than that previously demonstrated for physically based non-genetic viral diagnostic of enveloped viruses. These results are obtained by analysis of the original cell culture medium containing the virus, purified only by passage through a 0.22 µm filter and by dialysis into a 10 mM aqueous ammonium acetate buffer. We confirmed that this buffer exchange preserves infectivity. Therefore, the 63.7 nm mobility diameter found, although smaller than the 75 nm previously inferred by microscopy, corresponds to the full particle including the envelope.


Asunto(s)
Bacteriófagos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Virus , Diálisis Renal
17.
ACS Sens ; 6(9): 3445-3450, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34505501

RESUMEN

Accurate single virus detection is critical for disease diagnosis and early prevention, especially in view of current pandemics. Numerous detection methods have been proposed with the single virus sensitivity, including the optical approaches and immunoassays. However, few of them hitherto have the capability of both trapping and detection of single viruses in the microchannel. Here, we report an optofluidic potential well array to trap nanoparticles stably in the flow stream. The nanoparticle is bound with single viruses and fluorescence quantum dots through an immunolabeling protocol. Single viruses can be swiftly captured in the microchannel by optical forces and imaged by a camera. The number of viruses in solution and on each particle can be quantified via image processing. Our method can trap and detect single viruses in the 1 mL serum or water in 2 h, paving an avenue for the advanced, fast, and accurate clinical diagnosis, as well as the study of virus infectivity, mutation, drug inhibition, etc.


Asunto(s)
Micromanipulación , Virus , Micromanipulación/instrumentación , Virus/aislamiento & purificación
18.
Nat Commun ; 12(1): 5523, 2021 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-34535646

RESUMEN

RNA polymerase inhibition plays an important role in the regulation of transcription in response to environmental changes and in the virus-host relationship. Here we present the high-resolution structures of two such RNAP-inhibitor complexes that provide the structural bases underlying RNAP inhibition in archaea. The Acidianus two-tailed virus encodes the RIP factor that binds inside the DNA-binding channel of RNAP, inhibiting transcription by occlusion of binding sites for nucleic acid and the transcription initiation factor TFB. Infection with the Sulfolobus Turreted Icosahedral Virus induces the expression of the host factor TFS4, which binds in the RNAP funnel similarly to eukaryotic transcript cleavage factors. However, TFS4 allosterically induces a widening of the DNA-binding channel which disrupts trigger loop and bridge helix motifs. Importantly, the conformational changes induced by TFS4 are closely related to inactivated states of RNAP in other domains of life indicating a deep evolutionary conservation of allosteric RNAP inhibition.


Asunto(s)
ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , ARN Polimerasas Dirigidas por ADN/química , Virus/metabolismo , Regulación Alostérica , Secuencia de Aminoácidos , Proteínas Arqueales/metabolismo , Microscopía por Crioelectrón , ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/metabolismo , Modelos Moleculares , Unión Proteica , Estructura Secundaria de Proteína , Factores de Tiempo , Proteínas Virales/metabolismo , Viroides/metabolismo
20.
PLoS Biol ; 19(9): e3001390, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34582436

RESUMEN

Determining which animal viruses may be capable of infecting humans is currently intractable at the time of their discovery, precluding prioritization of high-risk viruses for early investigation and outbreak preparedness. Given the increasing use of genomics in virus discovery and the otherwise sparse knowledge of the biology of newly discovered viruses, we developed machine learning models that identify candidate zoonoses solely using signatures of host range encoded in viral genomes. Within a dataset of 861 viral species with known zoonotic status, our approach outperformed models based on the phylogenetic relatedness of viruses to known human-infecting viruses (area under the receiver operating characteristic curve [AUC] = 0.773), distinguishing high-risk viruses within families that contain a minority of human-infecting species and identifying putatively undetected or so far unrealized zoonoses. Analyses of the underpinnings of model predictions suggested the existence of generalizable features of viral genomes that are independent of virus taxonomic relationships and that may preadapt viruses to infect humans. Our model reduced a second set of 645 animal-associated viruses that were excluded from training to 272 high and 41 very high-risk candidate zoonoses and showed significantly elevated predicted zoonotic risk in viruses from nonhuman primates, but not other mammalian or avian host groups. A second application showed that our models could have identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a relatively high-risk coronavirus strain and that this prediction required no prior knowledge of zoonotic Severe Acute Respiratory Syndrome (SARS)-related coronaviruses. Genome-based zoonotic risk assessment provides a rapid, low-cost approach to enable evidence-driven virus surveillance and increases the feasibility of downstream biological and ecological characterization of viruses.


Asunto(s)
Predicción/métodos , Especificidad del Huésped/genética , Zoonosis/genética , Animales , COVID-19/genética , COVID-19/prevención & control , Brotes de Enfermedades/prevención & control , Genoma Viral/genética , Humanos , Aprendizaje Automático , Modelos Teóricos , Filogenia , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Virus/clasificación , Virus/genética , Zoonosis/clasificación , Zoonosis/virología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...