Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 30, 2024

Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue spread. Here, we show exhibits increased infectivity in primary adult upper airway tissue relative Delta. Using recombinant forms nasal epithelial cells cultured at the liquid-air interface, mutations unique Spike enable enhanced entry into tissue. Unlike earlier SARS-CoV-2, our findings suggest enters independently serine transmembrane proteases instead relies upon metalloproteinases catalyze membrane fusion. Furthermore, demonstrate this pathway unlocked by enables evasion from constitutive interferon-induced antiviral factors restrict attachment. Therefore, transmissibility exhibited humans may be attributed not only its vaccine-elicited adaptive immunity, but also superior invasion epithelia resistance cell-intrinsic barriers present therein.

Language: Английский

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Organoids and organoids-on-a-chip as the new testing strategies for environmental toxicology-applications & advantages

Environment International, Journal Year: 2024, Volume and Issue: 184, P. 108415 - 108415

Published: Jan. 8, 2024

An increasing number of harmful environmental factors are causing serious impacts on human health, and there is an urgent need to accurately identify the toxic effects mechanisms these factors. However, traditional toxicity test methods (e.g., animal models cell lines) often fail provide accurate results. Fortunately, organoids differentiated from stem cells can more accurately, sensitively specifically reflect body. They also suitable for specific studies frequently used in toxicology nowadays. As a combination organ-on-a-chip technology, organoids-on-a-chip has great potential toxicology. It controllable physicochemical microenvironment not easy be contaminated. higher homogeneity size shape organoids. In addition, it achieve vascularization exchange nutrients metabolic wastes time. Multi-organoids-chip simulate interactions different organs. These advantages facilitate better function maturity organoids, which make up shortcomings common certain extent. This review firstly discussed limitations testing platforms, leading introduction new platforms: organoids-on-a-chip. Next, applications were summarized prospected. Since platforms have been sufficiently considered previous literature, we particularly emphasized them. Finally, this opportunities challenges faced by organoids-on-a-chip, with expectation that readers will gain deeper understanding their value field

Language: Английский

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SARS-CoV-2 immunity in animal models

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(2), P. 119 - 133

Published: Jan. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Language: Английский

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Mucosal immune response in biology, disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 7, 2025

Abstract The mucosal immune system, as the most extensive peripheral network, serves frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion establishing tolerance. A comprehensive understanding immunity essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing overall impact on body. Despite its importance, our knowledge remains incomplete, necessitating further research. outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored critical role disease prevention treatment. This systematic review focuses dynamic interactions between mucosa-associated lymphoid structures related diseases. We delve into basic functions these tissues during processes explore intricate regulatory networks mechanisms involved. Additionally, we summarize novel therapies clinical research advances immunity-related also addresses challenges vaccines, which aim to induce specific responses while maintaining tolerance non-pathogenic microbes. Innovative therapies, such nanoparticle vaccines inhalable antibodies, show promise enhancing offer potential improved

Language: Английский

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Design and regulation of engineered bacteria for environmental release

Nature Microbiology, Journal Year: 2025, Volume and Issue: 10(2), P. 281 - 300

Published: Feb. 4, 2025

Language: Английский

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Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging comprehensively compare many spikes that emerged during pandemic a single experimental platform. Here we generated panel recombinant viruses carrying different proteins from 27 circulating between 2020 and 2024 same genomic background. We then assessed several phenotypic traits both vitro vivo. found distinct among before after emergence Omicron variants. Spike post-Omicron maintained enhanced tropism for nasal epithelium large airways but displayed, over time, typical pre-Omicron Hence, with features pre- may continue emerge future.

Language: Английский

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Intrahost evolution of the gut microbiota

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(9), P. 590 - 603

Published: April 17, 2023

Language: Английский

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Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet Respiratory Medicine, Journal Year: 2023, Volume and Issue: 11(12), P. 1075 - 1088

Published: Nov. 16, 2023

The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models is, to our knowledge, the first COVID-19 mucosal enter into human trials, but its efficacy is still unknown. We aimed assess safety (but not immunogenicity) of dNS1-RBD against COVID-19.

Language: Английский

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Mechanisms of SARS-CoV-2-associated anosmia

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2759 - 2766

Published: June 21, 2023

Anosmia, the loss of sense smell, is one main neurological manifestations COVID-19. Although SARS-CoV-2 virus targets nasal olfactory epithelium, current evidence suggests that neuronal infection extremely rare in both periphery and brain, prompting need for mechanistic models can explain widespread anosmia COVID-19 patients. Starting from work identifying non-neuronal cell types are infected by system, we review effects these supportive cells epithelium brain posit downstream mechanisms through which smell impaired We propose indirect contribute to altered system function COVID-19-associated anosmia, as opposed or neuroinvasion into brain. Such include tissue damage, inflammatory responses immune infiltration systemic circulation cytokines, downregulation odorant receptor genes sensory neurons response local signals. also highlight key unresolved questions raised recent findings.

Language: Английский

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A Mosaic Nanoparticle Vaccine Elicits Potent Mucosal Immune Response with Significant Cross‐Protection Activity against Multiple SARS‐CoV‐2 Sublineages

Advanced Science, Journal Year: 2023, Volume and Issue: 10(27)

Published: Aug. 1, 2023

Abstract Because of the rapid mutation and high airborne transmission SARS‐CoV‐2, a universal vaccine preventing infection in upper respiratory tract is particularly urgent. Here, mosaic receptor‐binding domain (RBD) nanoparticle (NP) developed, which induces more RBD‐targeted type IV neutralizing antibodies (NAbs) exhibits broad cross‐protective activity against multiple SARS‐CoV‐2 sublineages including newly‐emerged BF.7, BQ.1, XBB. As several T‐cell‐reactive epitopes, are highly conserved sarbecoviruses, displayed on NP surface, it also provokes potent cross‐reactive cellular immune responses tissue. Through intranasal delivery, elicits robust mucosal full protection without any adjuvants. Therefore, this can be further developed as pan‐sarbecovirus to block viral entrance from tract.

Language: Английский

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