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1.
Pak J Pharm Sci ; 36(3(Special)): 909-914, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37587697

RESUMEN

To observe the effect of amlodipine besylate combined with metoprolol in treating hypertension and heart failure. Total number of patients with hypertension combined with HF admitted to our hospital was One hundred and fifty from May 2017 to May 2022 selected for the study and they were distributed into single drug group and combination group by the method of random number table, with the total number of 75 cases in every group. Metoprolol treatment was given to the single drug group and metoprolol combined with amlodipine besylate treatment was given to the combination group. Both groups' scientific outcomes were compared, including their ventricular function, inflammatory factors, hemodynamics and liver and kidney function. Adverse treatment-related side events for patients were also tallied. Compared to the single drug group, the combination group's overall treatment effectiveness was higher (P<0.05). The combined group had better ventricular function, improved hemodynamics and lower levels of inflammatory factors (P<0.05). The liver, kidney function and adverse effects outcomes were the same in both groups (P>0.05). Amlodipine besylate combined with metoprolol has a better clinical effect in treating hypertension combined with heart failure, which can more effectively improve patients' cardiac function, inflammation and hemodynamics.


Asunto(s)
Insuficiencia Cardíaca , Hipertensión , Humanos , Metoprolol/efectos adversos , Amlodipino/efectos adversos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hemodinámica
2.
J Virol ; 92(13)2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29669833

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrelluscoronavirus HKU5, and MERS-related CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV.IMPORTANCE Previous studies suggested that MERS-CoV originated in bats. However, its evolutionary path from bats to humans remains unclear. In this study, we discovered 89 novel lineage C betacoronaviruses in eight bat species. We provide evidence of a MERS-related CoV derived from the great evening bat that uses the same host receptor as human MERS-CoV. This virus also provides evidence for a natural recombination event between the bat MERS-related CoV and another bat coronavirus, HKU4. Our study expands the host ranges of MERS-related CoV and represents an important step toward establishing bats as the natural reservoir of MERS-CoV. These findings may lead to improved epidemiological surveillance of MERS-CoV and the prevention and control of the spread of MERS-CoV to humans.


Asunto(s)
Quirópteros/virología , Infecciones por Coronavirus/veterinaria , Evolución Molecular , Genoma Viral , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Receptores Virales/metabolismo , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Quirópteros/genética , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Especificidad del Huésped , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/clasificación , Filogenia , Receptores Virales/genética , Homología de Secuencia , Proteínas Virales/genética
3.
Nature ; 503(7477): 535-8, 2013 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-24172901

RESUMEN

The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.


Asunto(s)
Quirópteros/virología , Peptidil-Dipeptidasa A/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , China , Chlorocebus aethiops , Reservorios de Enfermedades/virología , Heces/virología , Técnica del Anticuerpo Fluorescente , Genoma Viral/genética , Especificidad del Huésped , Humanos , Datos de Secuencia Molecular , Pandemias/prevención & control , Pandemias/veterinaria , Peptidil-Dipeptidasa A/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Virales/genética , Receptores Virales/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/ultraestructura , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/transmisión , Síndrome Respiratorio Agudo Grave/veterinaria , Síndrome Respiratorio Agudo Grave/virología , Especificidad de la Especie , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células Vero , Virión/aislamiento & purificación , Virión/ultraestructura , Internalización del Virus , Viverridae/metabolismo
4.
Virol J ; 13: 27, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26880191

RESUMEN

BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows highly genomic divergence.


Asunto(s)
Arvicolinae/virología , Infecciones por Hantavirus/veterinaria , Orthohantavirus/clasificación , Orthohantavirus/genética , Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/transmisión , Enfermedades de los Animales/virología , Animales , China/epidemiología , Reservorios de Enfermedades , Orthohantavirus/aislamiento & purificación , Ratones , Filogenia , ARN Viral , Análisis de Secuencia de ADN
5.
BMC Evol Biol ; 14: 154, 2014 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-25011626

RESUMEN

BACKGROUND: Hybrid zones formed by the secondary contact of divergent lineages represent natural laboratories for studying the genetic basis of speciation. Here we tested for patterns of differential introgression among three X-linked and 11 autosomal regions to identify candidate loci related to either reproductive isolation or adaptive introgression across a hybrid zone between two Chinese mainland subspecies of the intermediate horseshoe bat Rhinolophus affinis: R. a. himalayanus and R. a. macrurus. RESULTS: Our results support the previous suggestion that macrurus formed when a third subspecies (R. a. hainanus) recolonized the mainland from Hainan Island, and that himalayanus is the ancestral taxon. However, this overall evolutionary history was not reflected in all loci examined, with considerable locus-wise heterogeneity seen in gene tree topologies, levels of polymorphism, genetic differentiation and rates of introgression. Coalescent simulations suggested levels of lineage mixing seen at some nuclear loci might result from incomplete lineage sorting. Isolation with migration models supported evidence of gene flow across the hybrid zone at one intronic marker of the hearing gene Prestin. CONCLUSIONS: We suggest that phylogenetic discordance with respect to the species tree seen here is likely to arise via a combination of incomplete lineage sorting and a low incidence of introgression although we cannot rule out other explanations such as selection and recombination. Two X-linked loci and one autosomal locus were identified as candidate regions related to reproductive isolation across the hybrid zone. Our work highlights the importance of including multiple genomic regions in characterizing patterns of divergence and gene flow across a hybrid zone.


Asunto(s)
Quirópteros/genética , Animales , Núcleo Celular/genética , Quirópteros/clasificación , Quirópteros/fisiología , Cromosomas de los Mamíferos , ADN Mitocondrial/genética , Ecolocación , Flujo Génico , Genética de Población , Filogenia , Polimorfismo Genético , Aislamiento Reproductivo , Cromosoma X
6.
J Gen Virol ; 95(Pt 11): 2442-2449, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25034867

RESUMEN

Astroviruses infect humans and many animal species and cause gastroenteritis. To extensively understand the distribution and genetic diversity of astrovirus in small mammals, we tested 968 anal swabs from 39 animal species, most of which were bats and rodents. We detected diverse astroviruses in 10 bat species, including known bat astroviruses and a large number of novel viruses. Meanwhile, novel groups of astroviruses were identified in three wild rodent species and a remarkably high genetic diversity of astrovirus was revealed in Eothenomys cachinus. We detected astroviruses in captive-bred porcupines and a nearly full-length genome sequence was determined for one strain. Phylogenetic analysis of the complete ORF2 sequence suggested that this strain may share a common ancestor with porcine astrovirus type 2. Moreover, to our knowledge, this study reports the first discovery of astroviruses in shrews and pikas. Our results provide new insights for understanding these small mammals as natural reservoirs of astroviruses.


Asunto(s)
Mamastrovirus/genética , Mamastrovirus/aislamiento & purificación , Mamíferos/virología , Animales , Arvicolinae/virología , China , Quirópteros/virología , Variación Genética , Genoma Viral , Lagomorpha/virología , Mamastrovirus/clasificación , Datos de Secuencia Molecular , Filogenia , Roedores/virología , Musarañas/virología
7.
Arch Virol ; 159(6): 1359-64, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24357081

RESUMEN

H5N1 viruses cause severe and often fatal disease in humans. DNA vaccines have been shown to provide some protection in many animal models against H5N1 influenza virus infection, but this protection is not complete. To enhance the immunogenicity of an H5N1 DNA vaccine, we constructed the eukaryotic expression systems pcD-CD40 and pcD-HA. The expression of pcD-HA or pcD-CD40 in transfected BHK cells was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The constructs were then used to immunize BALB/c mice intramuscularly three times at two-week intervals. The titers of serum HA-specific antibodies were determined by ELISA, and the expression levels of the cytokines IL-2, IL-4, IL-6 and TNF-α were determined by real-time PCR. The results showed that CD40 as a molecular adjuvant significantly enhanced the production of serum anti-HA antibodies and increased the levels of the Th2 cytokines IL-4 and IL-6, suggesting that co-immunization with CD40 upregulated the humoral immune responses to the DNA vaccine in BALB/c mice. This study will provide important information for the selection of adjuvants for DNA vaccines against HPAI H5N1 viruses or other subtypes of human influenza viruses.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Antígenos CD40/administración & dosificación , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Vacunas de ADN/inmunología , Adyuvantes Inmunológicos/genética , Animales , Anticuerpos Antivirales/sangre , Antígenos CD40/genética , Citocinas/biosíntesis , Ensayo de Inmunoadsorción Enzimática , Perfilación de la Expresión Génica , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H5N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/genética , Inyecciones Intramusculares , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la Polimerasa , Vacunación/métodos , Vacunas de ADN/administración & dosificación , Vacunas de ADN/genética
8.
Open Med (Wars) ; 18(1): 20230821, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025544

RESUMEN

This study aims to analyze the effect of cardiac rehabilitation therapy on cardiac autonomic nervous function in patients with cardiac insufficiency complicated with anxiety depression after cardiac operation to provide a reference for clinical practice. A total of 109 patients subject to cardiac operation in our hospital from January 2020 to March 2023 were enrolled as study subjects, including 50 patients who received conventional rehabilitation therapy (control group) and 69 patients who received cardiac rehabilitation therapy (research group). Before and after treatment, the left ventricular ejection fraction (LVEF) and central venous pressure (CVP) were determined, and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured. Low frequency/high frequency (LF/HF), standard deviation of normal to normal (SDNN), and root mean of successive square differences (RMSSD) were measured by a multi-lead ECG system. Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Activity of daily living (ADL), and Barthel Index (BI) were applied for corresponding investigations, as well as the 6-min walk test (6MWT). After treatment, the research group showed higher LVEF, CVP, LF/HF, SDNN, and RMSSD, and lower NT-proBNP, SAS, and SDS than the control group (P < 0.05). Significantly elevated ADL score, BI, and 6MWT and reduced PSQI were observed in both groups after treatment, with more remarkable changes in the research group (P < 0.05). In conclusion, cardiac rehabilitation therapy effectively improved the cardiac function of patients with cardiac insufficiency complicated with anxiety and depression after the cardiac operation and alleviated their negative emotions.

9.
Breast Cancer Res Treat ; 136(3): 875-83, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23124417

RESUMEN

Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12, interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene activities. Recent work suggests that it may have effects on breast cancer progression and survival. We evaluated HOTAIR expression and the methylation status of its downstream intergenic CpG island in primary breast cancers, and examined associations of these factors with clinical and pathologic features and patient survival. HOTAIR expression and DNA methylation were analyzed in tissue from 348 primary breast cancers with quantitative RT-PCR and methylation-specific PCR, respectively. HOTAIR expression and methylation varied widely in the tissues. A positive correlation was found between DNA methylation and HOTAIR expression. Methylation was associated with unfavorable disease characteristics, whereas no significant associations were found between HOTAIR expression and clinical or pathologic features. In multivariate, but not in univariate, Cox proportional hazard regression models, patients with high HOTAIR expression had lower risks of relapse and mortality than those with low HOTAIR expression. These findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Islas de CpG , Metilación de ADN , ARN Largo no Codificante/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Somatomedinas/genética , Adulto Joven
10.
Mol Ecol ; 20(17): 3669-80, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21824210

RESUMEN

How males gain access to mates and the potential for female choice will determine whether polygyny can operate at several levels, from within litters and groups to the wider population. Female lesser flat-headed bats (Tylonycteris pachypus) form maternity groups in bamboo stems. Unusually for bats, they are multiparous, providing the opportunity to test whether multi-level polygyny differs among males depending on whether they roost with females, with males or are solitary. We genotyped 662 individuals from 54 internodes and analysed parentage of 165 litters. Our results revealed 170 sets of paternal twins/triplets, of which 96 were full-sibs and 74 were half-sibs. We found that males captured roosting with females typically sired more offspring overall than did other males and also showed a greater tendency to monopolize paternity within both litters and roosting groups. In comparison, males that sired fewer full-sibs were assigned more maternal half-sibs. These latter individuals, which included solitary males and those from all-male groups, might gain copulations either via roaming with furtive mating or during visits by females. Indeed, female lesser flat-headed bats store sperm, so could benefit from multiple mating to reduce genetic incompatibilities. At the same time, however, we found no evidence of outbreeding. Finally, relatedness and mtDNA analyses revealed that polygyny also operated within matrilineal kin, suggesting a system that might promote social cohesiveness. Future studies of individual movements will help to determine the extent to which mixed paternities in litters, matrilines and groups are driven by male or female behaviour.


Asunto(s)
Quirópteros/genética , ADN Mitocondrial/genética , Endogamia/métodos , Reproducción/genética , Conducta Sexual Animal , Animales , ADN/genética , ADN/aislamiento & purificación , Femenino , Genotipo , Masculino , Repeticiones de Microsatélite , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Espermatozoides
12.
Microbiome ; 9(1): 18, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478588

RESUMEN

BACKGROUND: As the largest group of mammalian species, which are also widely distributed all over the world, rodents are the natural reservoirs for many diverse zoonotic viruses. A comprehensive understanding of the core virome of diverse rodents should therefore assist in efforts to reduce the risk of future emergence or re-emergence of rodent-borne zoonotic pathogens. RESULTS: This study aimed to describe the viral range that could be detected in the lungs of rodents from Mainland Southeast Asia. Lung samples were collected from 3284 rodents and insectivores of the orders Rodentia, Scandentia, and Eulipotyphla in eighteen provinces of Thailand, Lao PDR, and Cambodia throughout 2006-2018. Meta-transcriptomic analysis was used to outline the unique spectral characteristics of the mammalian viruses within these lungs and the ecological and genetic imprints of the novel viruses. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time in these species, and viruses related to known pathogens were characterized for their genomic and evolutionary characteristics, host species, and locations. CONCLUSIONS: These results expand our understanding of the core viromes of rodents and insectivores from Mainland Southeast Asia and suggest that a high diversity of viruses remains to be found in rodent species of this area. These findings, combined with our previous virome data from China, increase our knowledge of the viral community in wildlife and arthropod vectors in emerging disease hotspots of East and Southeast Asia. Video abstract.


Asunto(s)
Pulmón/virología , ARN Viral/análisis , Roedores/virología , Viroma/genética , Animales , Asia Sudoriental , Insectos/virología
13.
Nanoscale Res Lett ; 15(1): 18, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31965340

RESUMEN

GeSn is a promising material for the fabrication of on-chip photonic and nanoelectronic devices. Processing techniques dedicated to GeSn have thus been developed, including epitaxy, annealing, ion implantation, and etching. In this work, suspended, strain-relaxed, and high-quality GeSn microdisks are realized by a new approach without any etching to GeSn alloy. The GeSn alloy was grown on pre-patterned Ge (001) substrate by molecular beam epitaxy at low temperatures. The transmission electron microscopy and scanning electron microscopy were carried out to determine the microstructures of the GeSn samples. The microdisks with different diameters of Ge pedestals were fabricated by controlling the selective wet etching time, and micro-Raman results show that the microdisks with different dimensions of the remaining Ge pedestals have different extents of strain relaxation. The compressive strain of microdisks is almost completely relaxed under suitable conditions. The semiconductor processing technology presented in this work can be an alternative method to fabricate innovative GeSn and other materials based micro/nano-structures for a range of Si-compatible photonics, 3D-MOSFETs, and microelectromechanical device applications.

15.
Int Health ; 12(2): 77-85, 2020 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-32040190

RESUMEN

BACKGROUND: Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS: Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS: Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human-animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS: This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses.


Asunto(s)
Animales Salvajes/virología , Enfermedades Transmisibles Emergentes/transmisión , Infecciones por Coronavirus/transmisión , Brotes de Enfermedades/prevención & control , Neumonía Viral/transmisión , Población Rural , Virosis/transmisión , Zoonosis/transmisión , Adolescente , Adulto , Animales , Betacoronavirus , COVID-19 , China/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Investigación Cualitativa , Factores de Riesgo , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave , Virosis/epidemiología , Adulto Joven , Zoonosis/epidemiología , Zoonosis/virología
16.
Nat Commun ; 11(1): 4235, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32843626

RESUMEN

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 630 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal. We find that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.


Asunto(s)
Quirópteros/virología , Infecciones por Coronavirus/veterinaria , Coronavirus/genética , Evolución Molecular , Zoonosis/transmisión , Animales , Teorema de Bayes , Betacoronavirus/clasificación , Betacoronavirus/genética , Biodiversidad , COVID-19 , China , Quirópteros/clasificación , Coronavirus/clasificación , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Humanos , Pandemias , Filogenia , Filogeografía , Neumonía Viral/transmisión , Neumonía Viral/virología , SARS-CoV-2 , Zoonosis/virología
17.
bioRxiv ; 2020 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-32577651

RESUMEN

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. We used a Bayesian statistical framework and sequence data from all known bat-CoVs (including 630 novel CoV sequences) to study their macroevolution, cross-species transmission, and dispersal in China. We find that host-switching was more frequent and across more distantly related host taxa in alpha-than beta-CoVs, and more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus . Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.

18.
Front Microbiol ; 10: 1900, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31474969

RESUMEN

Outbreaks of severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome in 2012 and fatal swine acute diarrhea syndrome in 2017 caused serious infectious diseases in humans and in livestock, resulting in serious public health threats and huge economic losses. All such coronaviruses (CoVs) were confirmed to originate from bats. To continuously monitor the epidemic-related CoVs in bats, virome analysis was used to classify CoVs from 831 bats of 15 species in Yunnan, Guangxi, and Sichuan Provinces between August 2016 and May 2017. We identified 11 CoV strains from 22 individual samples of four bat species. Identification of four alpha-CoVs from Scotophilus kuhlii in Guangxi, which was closely related to a previously reported bat CoV and porcine epidemic diarrhea virus (PEDV), revealed a bat-swine lineage under the genus Alphacoronavirus. A recombinant CoV showed that the PEDV probably originated from the CoV of S. kuhlii. Another alpha-CoV, α-YN2018, from Rhinolophus affinis in Yunnan, suggested that this alpha-CoV lineage had multiple host origins, and α-YN2018 had recombined with CoVs of other bat species over time. We identified five SARS-related CoVs (SARSr-CoVs) in Rhinolophus bats from Sichuan and Yunnan and confirmed that angiotensin-converting enzyme 2 usable SARSr-CoVs were continuously circulating in Rhinolophus spp. in Yunnan. The other beta-CoV, strain ß-GX2018, found in Cynopterus sphinx of Guangxi, represented an independently evolved lineage different from known CoVs of Rousettus and Eonycteris bats. The identification of diverse CoVs here provides new genetic data for understanding the distribution and source of pathogenic CoVs in China.

19.
Viruses ; 11(4)2019 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-31022925

RESUMEN

Bats have been identified as a natural reservoir of a variety of coronaviruses (CoVs). Several of them have caused diseases in humans and domestic animals by interspecies transmission. Considering the diversity of bat coronaviruses, bat species and populations, we expect to discover more bat CoVs through virus surveillance. In this study, we described a new member of alphaCoV (BtCoV/Rh/YN2012) in bats with unique genome features. Unique accessory genes, ORF4a and ORF4b were found between the spike gene and the envelope gene, while ORF8 gene was found downstream of the nucleocapsid gene. All the putative genes were further confirmed by reverse-transcription analyses. One unique gene at the 3' end of the BtCoV/Rh/YN2012 genome, ORF9, exhibits ~30% amino acid identity to ORF7a of the SARS-related coronavirus. Functional analysis showed ORF4a protein can activate IFN-ß production, whereas ORF3a can regulate NF-κB production. We also screened the spike-mediated virus entry using the spike-pseudotyped retroviruses system, although failed to find any fully permissive cells. Our results expand the knowledge on the genetic diversity of bat coronaviruses. Continuous screening of bat viruses will help us further understand the important role played by bats in coronavirus evolution and transmission.


Asunto(s)
Alphacoronavirus/clasificación , Quirópteros/virología , Infecciones por Coronavirus/veterinaria , Variación Genética , Genoma Viral , Proteínas Virales/genética , Alphacoronavirus/aislamiento & purificación , Animales , China , Infecciones por Coronavirus/virología , Evolución Molecular , Secuenciación de Nucleótidos de Alto Rendimiento , Sistemas de Lectura Abierta/genética , Filogenia , Análisis de Secuencia de ADN
20.
Biosaf Health ; 1(2): 84-90, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32501444

RESUMEN

Human interaction with animals has been implicated as a primary risk factor for several high impact zoonoses, including many bat-origin viral diseases. However the animal-to-human spillover events that lead to emerging diseases are rarely observed or clinically examined, and the link between specific interactions and spillover risk is poorly understood. To investigate this phenomenon, we conducted biological-behavioral surveillance among rural residents in Yunnan, Guangxi, and Guangdong districts of Southern China, where we have identified a number of SARS-related coronaviruses in bats. Serum samples were tested for four bat-borne coronaviruses using newly developed enzyme-linked immunosorbent assays (ELISA). Survey data were used to characterize associations between human-animal contact and bat coronavirus spillover risk. A total of 1,596 residents were enrolled in the study from 2015 to 2017. Nine participants (0.6%) tested positive for bat coronaviruses. 265 (17%) participants reported severe acute respiratory infections (SARI) and/or influenza-like illness (ILI) symptoms in the past year, which were associated with poultry, carnivore, rodent/shrew, or bat contact, with variability by family income and district of residence. This study provides serological evidence of bat coronavirus spillover in rural communities in Southern China. The low seroprevalence observed in this study suggests that bat coronavirus spillover is a rare event. Nonetheless, this study highlights associations between human-animal interaction and zoonotic spillover risk. These findings can be used to support targeted biological behavioral surveillance in high-risk geographic areas in order to reduce the risk of zoonotic disease emergence.

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