SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 5, 2023

ABSTRACT Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and tissue loss, raising concerns about virus’s potential chronic impact on central nervous system. In this study, we utilized mouse models human post-mortem tissues to investigate presence distribution SARS-CoV-2 spike protein in skull-meninges-brain axis. Our results revealed accumulation skull marrow, meninges, parenchyma. The injection alone cell death brain, highlighting direct effect tissue. Furthermore, observed deceased long after their COVID-19 infection, suggesting that spike’s persistence may contribute long-term symptoms. was neutrophil-related pathways dysregulation proteins involved PI3K-AKT as well complement coagulation pathway. Overall, our findings suggest trafficking from CNS borders into parenchyma identified differentially regulated present insights mechanisms underlying immediate consequences diagnostic therapeutic opportunities. Graphical Summary Short axis presents molecular targets for complications long-COVID-19 patients .

Язык: Английский

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Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19

Cell Host & Microbe, Год журнала: 2024, Номер 32(12), С. 2112 - 2130.e10

Опубликована: Ноя. 29, 2024

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed accumulation of spike protein in skull-meninges-brain axis human COVID-19 patients, persisting long after viral clearance. Further, biomarkers neurodegeneration were elevated cerebrospinal fluid from COVID proteomic analysis skull, meninges, brain samples revealed dysregulated inflammatory pathways neurodegeneration-associated changes. Similar distribution patterns SARS-CoV-2-infected mice. Injection alone was sufficient to induce neuroinflammation, proteome changes axis, anxiety-like behavior, exacerbated outcomes mouse models stroke traumatic injury. Vaccination reduced but did not eliminate Our findings suggest persistent at borders may contribute lasting sequelae COVID-19.

Язык: Английский

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Mapping the global interactome of the ARF family reveals spatial organization in cellular signaling pathways

Journal of Cell Science, Год журнала: 2024, Номер 137(9)

Опубликована: Апрель 12, 2024

ABSTRACT The ADP-ribosylation factors (ARFs) and ARF-like (ARL) GTPases serve as essential molecular switches governing a wide array of cellular processes. In this study, we used proximity-dependent biotin identification (BioID) to comprehensively map the interactome 28 out 29 ARF ARL proteins in two models. Through approach, identified ∼3000 high-confidence proximal interactors, enabling us assign subcellular localizations family members. Notably, uncovered previously undefined for ARL4D ARL10. Clustering analyses further exposed distinctiveness interactors with these GTPases. We also reveal that expression understudied member ARL14 is confined stomach intestines. phospholipase D1 (PLD1) ESCPE-1 complex, more precisely, SNX1, proximity interactors. Functional assays demonstrated can activate PLD1 cellulo involved cargo trafficking via complex. Overall, BioID data generated study provide valuable resource dissecting complexities spatial organization signaling.

Язык: Английский

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Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(16), С. 9341 - 9341

Опубликована: Авг. 19, 2022

Cyclophilin A (CypA), which has peptidyl-prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression several diseases, including inflammatory coronavirus infection, and cancer, activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, resistance, stem-like properties cancer is related poor prognosis patients with This review aims understand biology roles pathology targeting axis. To validate clinical significance interaction, we analyzed expression levels PPIA BSG genes encoding CD147, respectively, wide range tumor types using Cancer Genome Atlas (TCGA) database. We observed significant association between PPIA/BSG prognosis, such low survival rate high stage, types. Furthermore, was positively correlated many cancers. Therefore, this supports hypothesis that may improve treatment outcomes

Язык: Английский

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SARS-CoV-2 and male infertility: from short- to long-term impacts

Journal of Endocrinological Investigation, Год журнала: 2023, Номер 46(8), С. 1491 - 1507

Опубликована: Март 14, 2023

Язык: Английский

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SARS-CoV-2 Receptors and Their Involvement in Cell Infection

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Год журнала: 2023, Номер 17(1), С. 1 - 11

Опубликована: Март 1, 2023

Язык: Английский

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SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 4, 2024

T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While indicates an active anti-viral response, is sign of poor prognosis. T-cells, essence, rarely express ACE2 receptors, making cause cell depletion enigmatic. Moreover, emerging strains posed immunological challenge, potentially alarming for next pandemic. Herein, we review how possible indirect direct key mechanisms could contribute SARS-CoV-2-associated-lymphopenia. The fundamental mechanism inflammatory cytokine storm elicited by viral infection, which alters host metabolism into more acidic state. This "hyperlactic acidemia" together suppresses T-cell proliferation triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results shift from steady-state hematopoiesis stress hematopoiesis. Even low expression, presence cholesterol-rich lipid rafts on activated T-cells may enhance entry syncytia formation. Finally, indicate participation other receptors or auxiliary proteins that can work alone concert mechanisms. Therefore, address CD147-a novel route-for its new variants. CD147 not only expressed but it interacts co-partners orchestrate various biological processes. Given these features, appealing candidate pathogenicity. Understanding molecular cellular behind SARS-CoV-2-associated-lymphopenia will aid discovery potential therapeutic targets improve resilience our immune system against this rapidly evolving virus.

Язык: Английский

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The striking mimics between COVID-19 and malaria: A review

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 23, 2022

Objectives COVID-19 is a transmissible illness triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its onset in late 2019 Wuhan city of China, it continues to spread universally, leading an ongoing pandemic that shattered all efforts restrain it. On the other hand, Africa, infection may be influenced malaria coinfection. Hence, this review article, we aimed give comprehensive account similarities between and terms symptoms, clinical, immunological, molecular perspectives. Methodology In reviewed over 50 research papers highlight multilayered infections might influence ontology COVID-19. Results Despite poor health fragile medical system many sub-Saharan African countries, they persisted with statistically significantly low number cases. This was attributed factors such as young population age, warm weather, lack proper diagnosis, previous malaria, use antimalarial drugs, etc. Additionally, genetics appears play significant role shaping dynamics. evident recent genomic screening analyses angiotensin-converting enzyme (ACE2) malaria-associated-variants identified 6 candidate genes incidence severity. Moreover, clinical pathological resemblances two diseases have made considerable confusion diagnosis thereafter curb disease Africa. Therefore, possible regards pathological, genetical ascription were discussed. Conclusion Understanding dynamics Sub-Saharan Africa how shaped another endemic like can provide insights into tailor successful diagnostic, intervention, control plans lower both morbidity mortality.

Язык: Английский

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Endomembrane remodeling in SARS-CoV-2 infection

Cell Insight, Год журнала: 2022, Номер 1(3), С. 100031 - 100031

Опубликована: Май 17, 2022

During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the viral proteins intimately interact with host factors to remodel endomembrane system at various steps of lifecycle. The entry SARS-CoV-2 can be mediated by endocytosis-mediated internalization. Virus-containing endosomes then fuse lysosomes, in which S protein is cleaved trigger membrane fusion. Double-membrane vesicles generated from ER serve as platforms for replication and transcription. Virions are assembled ER–Golgi intermediate compartment released through secretory pathway and/or lysosome-mediated exocytosis. In this review, we will focus on how collaborate entry, replication, assembly egress. We also describe hijack cell surveillance system—the autophagic degradation pathway—to evade destruction benefit virus production. Finally, potential antiviral therapies targeting discussed.

Язык: Английский

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Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5664 - 5664

Опубликована: Март 16, 2023

Coronavirus disease COVID-19, which is caused by severe acute respiratory syndrome coronavirus SARS-CoV-2, has become a worldwide pandemic in recent years. In addition to being disease, COVID-19 'vascular disease' since it causes leaky vascular barrier and increases blood clotting elevating von Willebrand factor (vWF) levels the blood. this study, we analyzed vitro how SARS-CoV-2 spike protein S1 induces endothelial cell (EC) permeability its vWF secretion, underlying molecular mechanism for it. We showed that receptor-binding domain (RBD) sufficient induce vWF-secretion through angiotensin-converting enzyme (ACE)2 an ADP-ribosylation (ARF)6 activation-dependent manner. However, mutants, including those South African Californian variants of did not affect induced EC secretion. addition, have identified signaling cascade downstream ACE2 protein-induced secretion using pharmacological inhibitors. The knowledge gained from study could be useful developing novel drugs or repurposing existing treating infections particularly strains respond poorly vaccines.

Язык: Английский

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