Cyclophilin–CD147 interaction enables SARS-CoV-2 infection of human monocytes and their activation via Toll-like receptors 7 and 8

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Monocytes and macrophages, as important constituents of the innate immune system, are equipped with multiple Toll-like-receptors (TLRs) to recognize invading pathogens, such SARS-CoV-2, mount an antiviral response. Nevertheless, their uncontrolled activation can lead hyperinflammation seen in severe COVID-19. Surprisingly, we observed that recombinant SARS-CoV-2 Spike (S) Nucleocapsid (N) proteins triggered only a weak proinflammatory response human peripheral blood monocytes. By employing THP-1 Jurkat NF-κB::eGFP reporter cell lines expressing specific TLRs, various TLR ligands blocking antibodies, determined surface including TLR2/1, TLR2/6 TLR4 do not play major role sensing. However, monocytes potently activated by replication-competent correlates viral uptake is monocytes, but lymphocytes. We show monocyte involves two distinct steps. Firstly, infects process independent S protein prime receptor angiotensin-converting enzyme 2. Instead, alternative CD147, which highly expressed on recognizes its well-known interaction partners cyclophilins A B incorporated into virions. Secondly, upon via cyclophilin-CD147 interaction, be inhibited CD147 antibodies or competition cyclophilin B, RNA recognized TLR7/8 endosomes, leading upregulation tumor necrosis factor (TNF), interleukin (IL)-1β IL-6, comprising core hyperinflammatory signature. Taken together, our data reveal novel mechanism how sense suggest targeting axis might beneficial alleviate overt myeloid-driven inflammation infection.

Language: Английский

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Induction of the Inflammasome by the SARS‐CoV‐2 Accessory Protein ORF9b, Abrogated by Small‐Molecule ORF9b Homodimerization Inhibitors

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Viral accessory proteins play critical roles in viral escape from host innate immune responses and inflammatory pathogenesis. Here we show that the SARS‐CoV‐2 protein, ORF9b, but not other (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome‐dependent caspase‐1 A549 lung carcinoma cells THP‐1 monocyte‐macrophage cells. Exposure to lipopolysaccharide (LPS) ATP additively enhanced activation of by suggesting ORF9b LPS follow parallel pathways inflammasome caspase‐1. Following rational silico approaches, have designed small molecules capable inhibiting homodimerization which experimentally inhibited ORF9b‐ORF9b homotypic interactions, caused mitochondrial eviction ORF9b‐induced cells, cytokine release restored type I interferon (IFN‐I) signaling suppressed both cell models. These are first‐in‐class compounds targeting a protein for viral‐induced exacerbated inflammation responses, with potential mitigating severe immunopathogenic damage induced highly pathogenic coronaviruses restoring antiviral curtailed infection.

Language: Английский

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Basic implications on three pathways associated with SARS-CoV-2

Biomedical Journal, Journal Year: 2024, Volume and Issue: unknown, P. 100766 - 100766

Published: July 1, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus govern induction, resulting in multiorgan impacts. Its pathophysiology involves followings: 1) angiotensin-converting enzyme (ACE2) Toll-like receptor (TLR) pathways: 2) neuropilin (NRP) pathway: 3) spike protein pathway. Therefore, it is necessary to block pathological course with modulating innate lymphoid cells against diverse corona variants future.

Language: Английский

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Efficacy of Telerehabilitation Protocols for Improving Functionality in Post-COVID-19 Patients

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 44 - 44

Published: Jan. 1, 2025

Background and Aims: Telerehabilitation is essential for the recovery of post-COVID-19 patients, improving exercise tolerance, dyspnea, functional capacity, daily activity performance. This study aimed to describe telerehabilitation protocols specifically designed individuals with sequelae. Materials Methods: A systematic review was conducted registration number CRD42023423678, based on searches developed in following databases: ScienceDirect, Scopus, Dimensions.ai PubMed, using keywords such as “telerehabilitation” “COVID-19”. The final search date July 2024. selection studies involved an initial calibration process, followed by independent filtering researchers. criteria were applied prior critical appraisal, data extraction, risk bias assessment. Results: After reviewing 405 full-text papers, 14 articles included that focused interventions patients. These remote delivery protocols, vital sign monitoring, virtual supervision physical therapists. reported improvements function, muscle performance, lung psychological outcomes. Significant gains observed strength, mobility, well reductions fatigue, quality life, particularly social domains. Intervention aerobic, respiratory exercises, monitored tools heart rate monitors smartphones. Conclusions: positively impacts volumes, pulmonary capacities, dyspnea reduction, functionality, independence

Language: Английский

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SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signaling pathway to facilitate viral replication

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic RNA and also present various viral RNAs, where it plays a crucial role regulating life cycle. However, molecular mechanisms through which viruses regulate host m6A methylation are not fully understood. In this study, we reveal that SARS-CoV-2 HCoV-OC43 infection enhance by activating mTORC1 signaling pathway. Specifically, non-structural protein nsp14 upregulates expression of S-adenosylmethionine synthase MAT2A an mTORC1-dependent manner. This mTORC1-MAT2A axis subsequently stimulates synthesis (SAM). The increase SAM then enhances facilitates replication. Our findings uncover mechanism provide insights into how hijacks cellular epitranscriptomic modifications to promote its

Language: Английский

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Impaired inflammatory resolution with severe SARS-CoV-2 infection in leptin knock out obese hamster

iScience, Journal Year: 2025, Volume and Issue: unknown, P. 111837 - 111837

Published: Jan. 1, 2025

Comorbidities, such as obesity, increase the risk of severe COVID-19. However, mechanisms underlying illnesses in individuals with obesity are poorly understood. Here, we used gene-edited leptin knock out (Leptin -/-) obese hamsters to establish a infection model. This model exhibits robust viral replication, lung lesions, pronounced clinical symptoms, and fatal infection, mirroring COVID-19 patients obesity. Using single-cell transcriptomics on tissues pre- post-infection, found that monocyte-derived alveolar macrophages (MD-AM) play key role hyper-inflammation, including two unique MD-AM cell fate branches specific Leptin -/- hamsters. Notably, reduced Trem2-dependent efferocytosis pathways indicated weakened inflammation resolution, consistent scRNA-seq data from In summary, our study highlights obesity-associated SARS-CoV-2 infections establishes reliable preclinical animal for developing obesity-specific therapeutics critical

Language: Английский

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Co-infections and Reactivation of some Herpesviruses (HHV) and Measles Virus (MeV) in Egyptian Cancer Patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Journal of the Egyptian National Cancer Institute, Journal Year: 2025, Volume and Issue: 37(1)

Published: April 11, 2025

Abstract Background Coinfections and reactivation of persistent or latent viral infections such as herpesviruses (HHV) and/or measles virus (MeV) have been reported among COVID-19 patients. However, there is limited information regarding cancer patients who experienced severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The primary purpose this study was to investigate the interplay between SARS-CoV-2, HHV MeV in patients, aiming provide insights into pathophysiology these enhance patients’ health outcomes. Methods A prospective observational conducted on 4 groups ( n = 147): newly diagnosed infected with SARS-CoV-2 37), non-infected 13), apparently normal individuals 82) finally a control group 15). All samples were tested for infection using real-rime quantitative reverse transcription polymerase chain reaction (qRT-PCR). Antibody responses analyzed indirect enzyme-linked immunosorbent assay (ELISA), antibody levels compared controls. Potential re-activation investigated fourfold (i.e. 400%) rise model criterion. Results In all positive cases recent re-infection herpes simplex viruses 1 2 (HSV1/2 HHV1-2) found be significantly increased approximately three-fold higher p 0.007) identified via pooled HSV1/2 IgM plasma. Furthermore, 29.7% cancer/COVID-19 37) versus 0.0% normal/COVID-19 22) 0.008). Likewise, Epstein-Barr Nuclear Antigen-1 (EBNA-1) IgG showed ≥ increase 20% 0.034) 50) 4.9% controls 41) (EBV HHV-4). Obviously, up 78.0% 17.5% non-cancerous 40, < 0.001). Reactivation 43.2% 30.8% non-COVID-19 group, 3.3% COVID-19, healthy volunteers Conclusion Cancer at risk co-infection reactivation.

Language: Английский

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Computational Modeling of Transformations of Epidemic Waves of BA.2.86/JN.1 SAR-COV-2 Coronavirus Variants on the Basis of Hybrid Oscillators

Technical Physics, Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Language: Английский

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Advances in Understanding the Envelope Protein in Coronavirus Infection

Journal of Immunological Sciences, Journal Year: 2024, Volume and Issue: 8(1), P. 1 - 7

Published: May 7, 2024

The COVID-19 pandemic continues to impart devastating effects on human health, healthcare systems, and the economy. Vaccination, monoclonal antibodies, antiviral therapies prevent limit early infection. Unfortunately, few strategies exist mitigate disease burden in vast number of individuals who seek medical attention with established infection severe disease. While we have a limited understanding mechanistic basis by which SARS-CoV-2 causes critical illness, increasing evidence suggests that host-pathogen interactions shape immune responses drive pathogenesis COVID-19. Therefore, it is imperative understand roles viral proteins how they course One interesting protein envelope (E) SARS-CoV-2; this tiny structural has been implicated many phases life cycle. Importantly, E facilitates packaging replication, its deletion reduces pathogenicity. also possesses ion channel functions, interacts host proteins, potential various topologies. This review aims establish an updated highlighting recent developments investigation protein, particularly comparison SARS-CoV. thorough knowledge will enable targeted studies hopes tailored efficacious treatments.

Language: Английский

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The CoV-Y domain of SARS-CoV-2 Nsp3 interacts with BRAP to stimulate NF-κB signaling and induce host inflammatory responses

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 280, P. 136123 - 136123

Published: Sept. 28, 2024

Language: Английский

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