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1.
Viruses ; 12(6)2020 06 24.
Article in English | MEDLINE | ID: covidwho-620517

ABSTRACT

The respiratory Influenza A Viruses (IAVs) and emerging zoonotic viruses such as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pose a significant threat to human health. To accelerate our understanding of the host-pathogen response to respiratory viruses, the use of more complex in vitro systems such as normal human bronchial epithelial (NHBE) cell culture models has gained prominence as an alternative to animal models. NHBE cells were differentiated under air-liquid interface (ALI) conditions to form an in vitro pseudostratified epithelium. The responses of well-differentiated (wd) NHBE cells were examined following infection with the 2009 pandemic Influenza A/H1N1pdm09 strain or following challenge with the dsRNA mimic, poly(I:C). At 30 h postinfection with H1N1pdm09, the integrity of the airway epithelium was severely impaired and apical junction complex damage was exhibited by the disassembly of zona occludens-1 (ZO-1) from the cell cytoskeleton. wdNHBE cells produced an innate immune response to IAV-infection with increased transcription of pro- and anti-inflammatory cytokines and chemokines and the antiviral viperin but reduced expression of the mucin-encoding MUC5B, which may impair mucociliary clearance. Poly(I:C) produced similar responses to IAV, with the exception of MUC5B expression which was more than 3-fold higher than for control cells. This study demonstrates that wdNHBE cells are an appropriate ex-vivo model system to investigate the pathogenesis of respiratory viruses.


Subject(s)
Influenza A Virus, H1N1 Subtype/physiology , Influenza, Human/virology , Respiratory Mucosa/cytology , Respiratory Mucosa/virology , Animals , Bronchi/cytology , Bronchi/virology , Cells, Cultured , Chemokines/metabolism , Cytokines/metabolism , Dogs , Host-Pathogen Interactions , Humans , Immunity, Innate , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/epidemiology , Intercellular Junctions , Madin Darby Canine Kidney Cells , Models, Biological , Mucin 5AC/metabolism , Pandemics , Virus Cultivation
2.
BMC Infect Dis ; 20(1): 536, 2020 Jul 23.
Article in English | MEDLINE | ID: covidwho-670669

ABSTRACT

BACKGROUND: As the COVID-19 pandemic continues to spread, early, ideally real-time, identification of SARS-CoV-2 infected individuals is pivotal in interrupting infection chains. Volatile organic compounds produced during respiratory infections can cause specific scent imprints, which can be detected by trained dogs with a high rate of precision. METHODS: Eight detection dogs were trained for 1 week to detect saliva or tracheobronchial secretions of SARS-CoV-2 infected patients in a randomised, double-blinded and controlled study. RESULTS: The dogs were able to discriminate between samples of infected (positive) and non-infected (negative) individuals with average diagnostic sensitivity of 82.63% (95% confidence interval [CI]: 82.02-83.24%) and specificity of 96.35% (95% CI: 96.31-96.39%). During the presentation of 1012 randomised samples, the dogs achieved an overall average detection rate of 94% (±3.4%) with 157 correct indications of positive, 792 correct rejections of negative, 33 incorrect indications of negative or incorrect rejections of 30 positive sample presentations. CONCLUSIONS: These preliminary findings indicate that trained detection dogs can identify respiratory secretion samples from hospitalised and clinically diseased SARS-CoV-2 infected individuals by discriminating between samples from SARS-CoV-2 infected patients and negative controls. This data may form the basis for the reliable screening method of SARS-CoV-2 infected people.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Mass Screening/methods , Odorants/analysis , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Animals , Bronchi/chemistry , Bronchi/virology , Case-Control Studies , Dogs , Double-Blind Method , Humans , Pandemics/prevention & control , Pilot Projects , Saliva/chemistry , Saliva/virology , Sensitivity and Specificity
3.
Nature ; 583(7818): 834-838, 2020 07.
Article in English | MEDLINE | ID: covidwho-261141

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies1,2. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Models, Animal , Lung/pathology , Lung/virology , Mesocricetus/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Aerosols , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , Antigens, Viral/isolation & purification , Antigens, Viral/metabolism , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Betacoronavirus/metabolism , Bronchi/pathology , Bronchi/virology , Coronavirus Infections/immunology , Duodenum/virology , Fomites/virology , Housing, Animal , Kidney/virology , Male , Mesocricetus/immunology , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/immunology , RNA, Viral/analysis , Viral Load , Weight Loss
4.
Nature ; 583(7818): 830-833, 2020 07.
Article in English | MEDLINE | ID: covidwho-220333

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Coronavirus Infections/virology , Lung/pathology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Transgenes , Animals , Antigens, Viral/immunology , Antigens, Viral/metabolism , Betacoronavirus/immunology , Betacoronavirus/metabolism , Bronchi/pathology , Bronchi/virology , Coronavirus Infections/immunology , Disease Models, Animal , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Humans , Immunoglobulin G/immunology , Lung/immunology , Lung/virology , Lymphocytes/immunology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Male , Mice , Mice, Transgenic , Pandemics , Pneumonia, Viral/immunology , Receptors, Complement 3d/genetics , Receptors, Complement 3d/metabolism , Virus Replication , Weight Loss
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