SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 23, 2023

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice, neurons main target infection, neuronal progenitor cells immature infected. results herein suggest evolving may have increasing potential.

Language: Английский

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Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 13, 2024

Introduction Global microplastic (MP) pollution is now well recognized, with humans and animals consuming inhaling MPs on a daily basis, growing body of concern surrounding the potential impacts human health. Methods Using mouse model mild COVID-19, we describe herein effects azide-free 1 μm polystyrene MP beads, co-delivered into lungs SARS-CoV-2 omicron BA.5 inoculum. The effect host response to infection was analysed using histopathology RNA-Seq at 2 6 days post-infection (dpi). Results Although reduced clearance from lung, virus titres viral RNA levels were not significantly affected by MPs, overt MP-associated clinical or histopathological changes observed. However, infected revealed that exposure suppressed innate immune responses dpi increased pro-inflammatory signatures dpi. cytokine profile showed significant correlation ‘cytokine release syndrome’ signature observed in some COVID-19 patients. Discussion findings are consistent recent finding can inhibit phagocytosis apoptotic cells via binding Tim4. They also add literature suggesting dysregulate inflammatory processes specific disease settings.

Language: Английский

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Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(9), P. e1010867 - e1010867

Published: Sept. 26, 2022

How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified various settings. Herein we use RNA-Seq data bioinformatics approaches to analyze responses SARS-CoV-2 infected lungs, comparing 4 human studies widely used K18-hACE2 model, a model where hACE2 is expressed from ACE2 promoter, that uses adapted virus wild-type mice. Overlap of single copy orthologue differentially genes (scoDEGs) between was generally poor (≈15-35%). Rather than being associated batch, sample treatment, viral load, lung damage or overlaps were primarily due scoDEG expression differences species. Importantly, analyses immune signatures inflammatory pathways illustrated highly significant concordances As immunity immunopathology are focus most studies, these can thus be viewed as representative relevant COVID-19.

Language: Английский

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SARS-CoV-2 variants: Impact on biological and clinical outcome

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 10, 2022

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first identified in December 2019, Wuhan, China found to be the etiological agent for a novel infection led Coronavirus Induced Disease named COVID-19. disease spread pandemic magnitudes within few weeks and since then we have been dealing with several waves across world, due emergence of variants mutations this RNA virus. A direct outcome these apart from spike cases is diverse presentation difficulty employing effective diagnostic tools confusing outcomes. Transmissibility rates variants, host response, virus evolution are some features impact COVID-19 management. In review, will discuss emerging SARS-CoV-2, notable viral genome, possible on detection, presentation, management as well recent findings mechanisms underlie virus-host interaction. Our aim invigorate scientific debate how pathogenic potential new strains contributes toward development field virology general particular.

Language: Английский

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TMEM106B-mediated SARS-CoV-2 infection allows for robust ACE2-independent infection in vitro but not in vivo

Cell Reports, Journal Year: 2024, Volume and Issue: 43(11), P. 114921 - 114921

Published: Nov. 1, 2024

Angiotensin-converting enzyme 2 (ACE2) is the primary entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV-2), but ACE2-independent has been observed in vitro strains with spike-E484D substitution. Here, we conduct a whole-genome CRISPR-Cas9 knockout screen using SARS-CoV-2 mouse adapted 1 (SARS-CoV-2

Language: Английский

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Warmer ambient air temperatures reduce nasal turbinate and brain infection, but increase lung inflammation in the K18-hACE2 mouse model of COVID-19

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 859, P. 160163 - 160163

Published: Nov. 14, 2022

Warmer climatic conditions have been associated with fewer COVID-19 cases. Herein we infected K18-hACE2 mice housed at the standard animal house temperature of ∼22 °C, or ∼31 which is considered to be thermoneutral for mice. On day 2 post infection, RNA-Seq analyses showed no significant differential gene expression lung in lungs two temperatures, almost identical viral loads and type I interferon responses. There was also difference on 5, but histology clearly elevated inflammatory signatures infiltrates. Thermoneutrality thus promoted inflammation. infection 31 °C reduced nasal turbinates, consistent increased mucociliary clearance warmer ambient temperature. These had virus levels brain, an ensuing amelioration weight loss a delay mortality. air temperatures may reduce upper respiratory track olfactory epithelium, resulting brain infection. Potential relevance anosmia neurological sequelae patients discussed.

Language: Английский

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Defective Interfering Particles with Broad-Acting Antiviral Activity for Dengue, Zika, Yellow Fever, Respiratory Syncytial and SARS-CoV-2 Virus Infection

Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(6)

Published: Nov. 29, 2022

More than 100 arboviruses, almost all of which have an RNA genome, cause disease in humans. viruses are causing unprecedented health system challenges worldwide, many with little or no specific therapies vaccines available. Certain species mosquito can carry dengue virus (DENV), Zika (ZIKV) and yellow fever (YFV), where co-infection these has occurred. Here, we found that purified synthetic defective interfering particles (DIPs) derived from DENV type 2 (DENV-2) strongly suppressed replication the aforementioned viruses, respiratory syncytial (RSV) also novel emerging SARS-CoV-2 human cells. DIPs produced bioreactors, by column chromatography, concentrated virus-like about half diameter a typical particle, but similar ratios viral structural proteins envelope capsid. Overall, DIP-treated cells inhibited DENV, ZIKV, YFV, RSV, at least 98% mechanisms included interferon (IFN)-dependent cellular antiviral responses.

Language: Английский

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Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern

Viruses, Journal Year: 2022, Volume and Issue: 15(1), P. 139 - 139

Published: Dec. 31, 2022

The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) has spawned an ongoing demand for new research reagents and interventions. Herein we describe a panel of monoclonal antibodies raised against SARS-CoV-2. One antibody showed excellent utility immunohistochemistry, clearly staining infected cells in formalin-fixed paraffin embedded lungs brains mice with original omicron variants We demonstrate reactivity to multiple concern using ELISAs use indirect immunofluorescence assays, Western blots, rapid antigen tests. Finally, illustrate ability two reduce significantly viral tissue titers K18-hACE2 transgenic isolate

Language: Английский

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Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in disease, often characterised by a ‘cytokine storm’ and the associated distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout course of infection. Although blood biomarkers disease well studied, less understood inflammatory signatures lung tissues silent infections, wherein infection inflammation rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq histological analyses lungs over time an omicron BA.1/K18-hACE2 mouse model, displays these latter features. robust was evident at days post (dpi), viral RNA largely cleared 10 dpi. Acute showed slightly different pattern cytokine compared models, where much diminished 30 dpi absent 66 Cellular deconvolution identified significantly increased abundance scores for number anti-inflammatory pro-resolution cell types 5/10 These included type II innate lymphoid cells, T regulatory interstitial macrophages. Genes whose expression trended downwards – were pathways. upward during this period recovery ciliated AT2 AT1 transition, reticular fibroblasts indicating return homeostasis. Very few differentially expressed host genes dpi, suggesting near complete parallels between subclinical humans those observed model discussed reference concept “protective inflammation”.

Language: Английский

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Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

ABSTRACT The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether cellular proteins ASGR1, DC-SIGN, TMEM106B, which interact with S protein, contribute to these processes. Employing protein-pseudotyped particles, found that expression ASGR1 or DC-SIGN jointly TMEM106B allowed for robust mutant into otherwise non-susceptible cells, while this effect was not observed upon separate single infection SARS-CoV-2 wild type (WT). Furthermore, conferred independence resistance but WT, under those conditions dependent on endogenous TMEM106B. These results suggest engagement certain lectins direct an ACE2-independent, TMEM106B-dependent pathway is inhibited by imdevimab. IMPORTANCE interaction receptor determines cell tropism key target neutralizing antibody response. show a single, E484D, use conjunction ACE2-independent evasion therapeutic antibodies. might modulate choice allow

Language: Английский

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