SARS‐CoV‐2 Productively Infects Human Hepatocytes and Induces Cell Death

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 1, 2025

SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing conditions experience more severe disease. While it was known that infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication spread, highlights direct hepatocyte damage. Viral readily detectable upon primary hepatocytes hepatoma cells ancestral SARS-CoV-2, Delta, Omicron variants. Hepatocytes express receptor ACE2 host cell protease TMPRSS2, knocking down TMPRSS2 impaired infection. Progeny viruses released from infected showed typical coronavirus morphology electron microscopy proved infectious when transferred to fresh cells, indicating can contribute virus spread. Importantly, rapidly induced death in a replication-dependent fashion, variant showing faster onset but less extensive death. C57BL/6 wild-type mice mouse-adapted strain high levels RNA lung tissues. ALT peaked cleared liver. Liver histology revealed profound tissue damage immune infiltration, cytopathic effects immune-mediated killing pathology.

Language: Английский

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Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 135 - 135

Published: Jan. 15, 2025

The study of pathogenic viruses has always posed significant biosafety challenges. In particular, the highly requires methods with low biological risk but relatively high sensitivity and convenience in detection. recent years, pseudoviruses, which consist a backbone one virus envelope proteins another virus, have become most widely used tools for exploring mechanisms binding to cells, membrane fusion viral entry, as well screening libraries antiviral substances, evaluating potential neutralizing monoclonal antibodies, developing neutralization tests, therapeutic platforms. During outbreak severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pseudotyped virus-based assays played pivotal role advancing our understanding virus-cell interactions its disease pathogenesis. Such facilitated search agents accelerated epidemiological studies on post-infection post-vaccination humoral immunity. This review focuses use pseudoviruses model large-scale applications enveloped viruses.

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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CRISPR-Cas: a game-changer in vaccine development and the fight against viral infections

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Classification of C‐Type Lectins and Recognition of Pathogens

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

Published: March 12, 2025

ABSTRACT C‐type lectins are calcium‐dependent glycan‐binding proteins that play key roles in the innate immune response by recognizing pathogens. Soluble agglutinate and neutralize pathogens, activate complement system, promote pathogen clearance via opsonization. Membrane‐bound lectins, also known as lectin receptors (CLRs), internalize pathogens induce their degradation lysosomes, presenting pathogen‐derived antigens to MHC‐II molecules adaptive immunity. CLRs have signaling capabilities. Some contain immunoreceptor tyrosine‐based activation motif (ITAM), which induces inflammatory responses activating transcription factors, such NF‐κB NFAT. Others inhibitory (ITIM), suppresses signals phosphatases, SHP‐1. This creates a balance between inhibition. classified into 17 groups based on structural domains, with Groups II V members being particularly important for recognition. In this review, we present accumulated recent information recognition along classification basic functions.

Language: Английский

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A survey of SARS-CoV-2 tropism

Infectious Diseases & Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has significantly burdened global public health. However, the tropism of SARS-CoV-2 within human body remains not fully understood. In this review, we overview literature on infection across various organs and tissues. We summarize relevant specimen types, techniques for examining tropism, findings at both organ/tissue cellular levels. To systematically evaluate evidence supporting tissue establish a hierarchical classification system based two key criteria: (1) origin (2) detection methodology. Clinical specimens obtained directly from COVID-19 patients provide most definitive evidence, whereas organoid-derived animal models indicate potential infectivity under artificial conditions. terms methods, prioritize viral particle identification over protein or RNA detection, as latter requires further confirmation to productive infection. Our that potentially targets multiple organ systems, including tract, lungs, kidneys, heart, blood vessels, pancreas, small intestine, liver, salivary glands. By contrast, central nervous reproductive uncertain validation. At level, identify specific target cell types vulnerable infection, ciliated epithelial cells, alveolar type II pneumocytes, enterocytes, cardiomyocytes, vascular endothelial renal tubular pancreatic acinar cells. Furthermore, analyze correlation between angiotensin-converting enzyme receptor distribution patterns well variations in specificity among different variants. expect review comprehensive landscape enhance our understanding life cycle consequences body.

Language: Английский

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The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9635 - 9635

Published: Sept. 5, 2024

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors discovered. Their functioning provide an explanation for some the events observed COVID-19 cannot be directly explained by model which ACE2 constitutes central point infection. Diabetes mellitus type (T2D) can induce development. Although mechanisms associated with lead increased SARS-CoV-2 virulence diabetes, such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster differentiation 4 (CD4), transferrin (TfR), integrins α5β1/αvβ3, or co-receptors neuropilin (NRP2), vimentin, and even syalilated gangliosides also responsible worsening course. On hand, others play protective roles. Understanding how diabetes-associated via modification needs further extensive studies.

Language: Английский

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Beyond conventional treatment: ASGR1 Leading the new era of hypercholesterolemia management

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117488 - 117488

Published: Sept. 23, 2024

Language: Английский

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Combination of spatial transcriptomics analysis and retrospective study reveals liver infection of SARS-COV-2 is associated with clinical outcomes of COVID-19

EBioMedicine, Journal Year: 2024, Volume and Issue: 111, P. 105517 - 105517

Published: Dec. 21, 2024

Language: Английский

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TurboID-mediated proximity labeling technologies to identify virus co-receptors

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: June 27, 2024

Virus receptors determine the tissue tropism of viruses and have a certain relationship with clinical outcomes caused by viral infection, which is great importance for identification virus to understand infection mechanism develop entry inhibitor. Proximity labeling (PL) new technique studying protein-protein interactions, but it has not yet been applied or co-receptors. Here, we attempt identify co-receptor SARS-CoV-2 employing TurboID-catalyzed PL. The membrane protein angiotensin-converting enzyme 2 (ACE2) was employed as bait conjugated TurboID, A549 cell line stable expression ACE2-TurboID constructed. pseudovirus were incubated stably expressed lines in presence biotin ATP, could initiate catalytic activity TurboID tag adjacent endogenous proteins biotin. Subsequently, biotinylated harvested identified mass spectrometry. We protein, AXL, that functionally shown mediate into host cells. Our data suggest PL be used co-receptors entry.

Language: Английский

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