Nature communications
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Nature communications · Aug 2020
A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge.
The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.
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Nature communications · Aug 2020
Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic.
The ongoing novel coronavirus disease (COVID-19) pandemic has already infected millions worldwide and, with no vaccine available, interventions to mitigate transmission are urgently needed. While there is broad agreement that travel restrictions and social distancing are beneficial in limiting spread, recommendations around face mask use are inconsistent. ⋯ However, random distribution of masks is generally suboptimal; prioritized coverage of the elderly improves outcomes, while retaining resources for detected cases provides further mitigation under a range of scenarios. Face mask use, particularly for a pathogen with relatively common asymptomatic carriage, is an effective intervention strategy, while optimized distribution is important when resources are limited.
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Nature communications · Jul 2020
Activation and evasion of type I interferon responses by SARS-CoV-2.
The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between the viral pathogen of COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. ⋯ Further analyses suggest that ORF6 inhibits both type I IFN production and downstream signaling, and that the C-terminus region of ORF6 is critical for its antagonistic effect. Finally, we find that IFN-β treatment effectively blocks SARS-CoV-2 replication. In summary, our study shows that SARS-CoV-2 perturbs host innate immune response via both its structural and nonstructural proteins, and thus provides insights into the pathogenesis of SARS-CoV-2.
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Nature communications · Jul 2020
MG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling.
TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. ⋯ We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury.