Ontology highlight
ABSTRACT:
PROVIDER: PRJNA769148 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16227939_1.fastq.gz | Fastqsanger.gz | |||
| SRR16227939_2.fastq.gz | Fastqsanger.gz | |||
| SRR16227940_1.fastq.gz | Fastqsanger.gz | |||
| SRR16227940_2.fastq.gz | Fastqsanger.gz | |||
| SRR16227941_1.fastq.gz | Fastqsanger.gz |
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Project description:All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801?an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials?markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
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Project description:BACKGROUND: 50% to 80% of asthma exacerbations are precipitated by viral upper respiratory tract infections (RTI), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood due to the limited scope and throughput of conventional viral detection methods. METHODS: We investigated the capability of the Virochip, a DNA microarray-based viral detection platform, to characterize the viral diversity in RTIs in asthmatic and non-asthmatic adults. RESULTS: The Virochip detected viruses in a higher proportion of samples (65%) than culture isolation (17%), while exhibiting high concordance (98%), sensitivity (97%) and specificity (98%) with pathogen-specific PCR. A similar spectrum of viruses was identified in the RTIs from each patient subgroup; however, unexpected diversity among the coronaviruses (HCoVs) and HRVs was revealed. All but one of the HCoVs corresponded to the newly-recognized HCoV-NL63 and HCoV-HKU1 viruses, and over 20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that form a distinct genetic subgroup. CONCLUSIONS: The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger scale studies will be necessary to determine if particular substrains of viruses confer an elevated risk of asthma exacerbation Keywords: Virus detection
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Project description:BACKGROUND: 50% to 80% of asthma exacerbations are precipitated by viral upper respiratory tract infections (RTI), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood due to the limited scope and throughput of conventional viral detection methods. METHODS: We investigated the capability of the Virochip, a DNA microarray-based viral detection platform, to characterize the viral diversity in RTIs in asthmatic and non-asthmatic adults. RESULTS: The Virochip detected viruses in a higher proportion of samples (65%) than culture isolation (17%), while exhibiting high concordance (98%), sensitivity (97%) and specificity (98%) with pathogen-specific PCR. A similar spectrum of viruses was identified in the RTIs from each patient subgroup; however, unexpected diversity among the coronaviruses (HCoVs) and HRVs was revealed. All but one of the HCoVs corresponded to the newly-recognized HCoV-NL63 and HCoV-HKU1 viruses, and over 20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that form a distinct genetic subgroup. CONCLUSIONS: The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger scale studies will be necessary to determine if particular substrains of viruses confer an elevated risk of asthma exacerbation This SuperSeries is composed of the SubSeries listed below.
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