Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus

PLoS Pathogens, Год журнала: 2023, Номер 19(7), С. e1011052 - e1011052

Опубликована: Июль 28, 2023

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result several metabolic disorders genotypes have been associated with multiple diseases. is synthesized at the endoplasmic reticulum transported to Golgi apparatus for LP assembly; however, ApoE-LPs pathway from there membrane largely unknown. Here, we established an integrative imaging approach based on a fully functional fluorescently tagged ApoE. We found that newly accumulate CD63-positive endosomes hepatocytes. In addition, observed co-egress intraluminal vesicles (ILVs), which are precursors extracellular (EVs), along late endosomal trafficking route microtubule-dependent manner. A fraction EVs appears be co-transmitted cell cell. Given important role viral infections, employed as well-studied model hepatitis C virus (HCV) replicase component nonstructural protein 5A (NS5A) enriched ApoE-containing ILVs. Interaction between NS5A required efficient release ILVs containing HCV RNA. These egress pathway. Taken together, our data argue transmission hepatic ApoE-LPs, hijacked by HCV. more general EV-mediated cell-to-cell communication, these insights provide new starting points research into pathophysiology ApoE-related infection-related disorders.

Язык: Английский

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Coupling of Alzheimer’s Disease Genetic Risk Factors with Viral Susceptibility and Inflammation

Aging and Disease, Год журнала: 2023, Номер 15(5), С. 2028 - 2028

Опубликована: Окт. 21, 2023

Alzheimer's disease (AD) is a neurodegenerative characterized by persistent cognitive decline. Amyloid plaque deposition and neurofibrillary tangles are the main pathological features of AD brain, though mechanisms leading to formation lesions remain be understood. Genetic efforts through genome-wide association studies (GWAS) have identified dozens risk genes influencing pathogenesis progression AD, some which been revealed in close with increased viral susceptibilities abnormal inflammatory responses patients. In present study, we try list candidate that shown affect infection responses. Understanding how susceptibility interact life cycle potential pathways would provide possible therapeutic targets for both infectious diseases.

Язык: Английский

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Oxylipin transport by lipoprotein particles and its functional implications for cardiometabolic and neurological disorders

Progress in Lipid Research, Год журнала: 2023, Номер 93, С. 101265 - 101265

Опубликована: Ноя. 17, 2023

Lipoprotein metabolism is critical to inflammation. While the periphery and central nervous system (CNS) have separate yet connected lipoprotein systems, impaired implicated in both cardiometabolic neurological disorders. Despite substantial investigation into composition, structure function of lipoproteins, oxylipin profiles, their influence on functions, potential biological implications are unclear. Lipoproteins carry most circulating oxylipins. Importantly, lipoprotein-mediated transport allows for endocrine signaling by these lipid mediators, long considered only autocrine paracrine functions. Alterations plasma composition can directly impact inflammatory responses metabolizing cells. Similar investigations CNS oxylipins non-existent date. However, as APOE4 associated with Alzheimer's disease-related microglia dysfunction dysregulation, ApoE4-dependent modulation pathologies suggested. Such crucial bridge knowledge gaps linking oxylipin- lipoprotein-related disorders CNS. Here, after providing a summary existent literatures analysis methods, we emphasize importance lipoproteins argue that understanding compartmentalization distribution may fundamentally alter our consideration roles

Язык: Английский

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Post-COVID-19 Cognitive Decline and Apoe Polymorphism: Towards a Possible Link?

Brain Sciences, Год журнала: 2023, Номер 13(12), С. 1611 - 1611

Опубликована: Ноя. 21, 2023

APOE ε4 polymorphism has been recently described as a possible association with cognitive deficits in COVID-19 patients. This research aimed to establish the correlation between and impairment, gene among outpatients. We performed cross-sectional study confirmed patients neurological symptoms that persisted for more than three months from onset. genotypes were determined. The final number of included this was 219, which 186 blood samples collected genotyping, evaluated 4.5 after COVID-19. Among participants, 143 (65.3%) reported memory impairment their primary concern. However, complaint objectively verified through screening tests (Addenbrooke Cognitive Examination-Revised Mini-Mental State Examination) only 36 (16.4%). group experiencing decline exhibited higher prevalence allele normal (30.8% vs. 16.4%, respectively, p = 0.038). Furthermore, anxiety remained significant multivariate analysis. assessed an outpatient population where changes complaint, even mild cases. Moreover, allele, sleep disorders, frequent group.

Язык: Английский

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Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing

Heliyon, Год журнала: 2024, Номер 10(7), С. e28280 - e28280

Опубликована: Март 16, 2024

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted lives of affected patients. However, involvement four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, in cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data seven tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid (PG), tongue, gingiva, buccal, periodontium pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell scCancer packages were comprehensively used for analysis. identified specific cell clusters generated expression profiles SARS-CoV-2 coronavirus-associated receptors factors (SCARFs) regions, providing direction predicting tropism HCoVs tissues, as well dental clinical treatment. Based on our analysis, it appears various SCARFs, ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, TMPRSS11A), FURIN, are expressed at low levels cavity. Conversely, BSG, CTSB, CTSL exhibit enrichment tissues. Our study also demonstrates widespread restriction factors, particularly IFITM1-3 LY6E, cells. Additionally, some replication, assembly, trafficking appear to broad patterns. Overall, could potentially serve a high-risk site infection, while displaying comparatively lower degree susceptibility towards other MERS-CoV HCoV-229E). Specifically, MSG, gingiva represent potential sites vulnerability with MSG exhibiting high susceptibility. patterns SCARFs demonstrate relatively intricate may only be specifically associated infection. sheds light mechanisms infection gains insight into characteristics distribution possible target cells therapeutic targets

Язык: Английский

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