NRF2-mediated regulation of lipid pathways in viral infection

Molecular Aspects of Medicine, Год журнала: 2024, Номер 97, С. 101279 - 101279

Опубликована: Май 20, 2024

Язык: Английский

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Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 25, 2023

Abstract The crucial role of interferon (IFN) signaling is well known in the restriction or eradication pathogen invasion. Viruses take a variety ways to antagonize host defense through eliminating IFN-signaling intracellularly for decades. However, way by viruses target extracellularly has not been discovered. Infection both coronavirus SARS-CoV-2 and enterovirus 71 (EV71 EV-A71) can cause severe diseases such as neurological disorders even death children. 1–3 Here, we show evidence that protease (3CL pro ) EV71 (2A upregulates expression secretion LDL - receptor-related protein-associated protein 1 (LRPAP1). As ligand, N-terminus secreted LRPAP1 binds with extracellular domain IFNAR1 triggers receptor ubiquitination degradation promotes virus infection vitro, ex vivo mouse brain, newborn mice. A small peptide from effectively causes enhances DNA RNA viral infections, including herpesvirus HSV-1, hepatitis B (HBV), EV71, beta-coronavirus HCoV-OC43; whereas α2M, inhibitor, arrests infections stabilizing IFNAR1. Our study demonstrates new mechanism used evading cell immunity, supporting strategy developing pan-antiviral drugs.

Язык: Английский

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HDL-based therapeutics: A promising frontier in combating viral and bacterial infections

Pharmacology & Therapeutics, Год журнала: 2024, Номер 260, С. 108684 - 108684

Опубликована: Июль 2, 2024

Язык: Английский

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Identification of NTCP animal orthologs supporting hepatitis B virus binding and infection

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Hepatitis B virus (HBV) infection is a significant global health threat, resulting in more than 800,000 deaths annually. Since HBV naturally infects only humans and chimpanzees, the development evaluation of new therapies for chronic are hindered by lack suitable animal models. Human sodium-taurocholate cotransporting polypeptide (NTCP) critical factor binding entry, exhibiting species-specific differences amino acid sequences. This study investigated NTCP orthologs from various species to determine their capability support infection. We demonstrate that nonhuman woodchuck, ferret, aardvark, horse, rabbit, whale, big brown bat, cat, rhinoceros cellular thereby rendering HepG2 cells susceptible upon expression. hamster, goat, cow but require specific exchanges facilitate show replacement functional region, acids (aa) 84-87, hamster with human counterpart allows expressing chimeric variant. Furthermore, we aa 82 goat NTCP, close this needs be modified could help identify previously unknown reservoirs may establishment models.IMPORTANCEThe bona fide entry receptor provides natural barrier cross-species transmission. identified orthologues reveal potential

Язык: Английский

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Discovery of novel HBV core protein inhibitors by high throughput virtual screening

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 16, 2025

Hepatitis B Virus (HBV) constitutes a chronic viral infection with limited therapeutic options and significant global health challenge. The virus lifecycle intricacy significantly relies on the core protein crucial for structure stability interaction host cells thus contributing to infection's persistence severity. This study employs advanced techniques identification of novel inhibitors through screening two chemical databases ZINC BIMP utilizing computational methods such as structure-based virtual screening, drug-likeness, ADME, toxicity, consensus molecular docking, density functional theory, 100 ns dynamics simulation. compound ZINC00674395 possesses high affinity specificity towards demonstrating drug-like properties, favorable ADME profiles, non-toxicity, electronic configuration at active site highlighting its potential agent. These findings offer new insights into pave way developing effective HBV therapeutics.

Язык: Английский

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Innate immune recognition in hepatitis B virus infection

Virulence, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 20, 2025

Hepatitis B virus (HBV) remains a major global public health challenge, with approximately 254 million individuals chronically infected worldwide. The interaction between HBV and the innate immune system has garnered significant attention within scientific community, numerous studies exploring this relationship over past several decades. While some research suggests that infection activates host's response, other indicate suppresses signaling pathways. These conflicting findings underscore complexity of HBV-innate immunity interaction, which inadequately understood. This review aims to clarify interplay by examining it from three perspectives: (a) showing activation immunity; (b) evidence suggesting suppression (c) support HBV's role as stealth virus. By synthesizing these perspectives, we aim deepen understanding virus-host interactions are crucial persistence evasion, potential implications for developing new therapeutic strategies chronic infection.

Язык: Английский

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Recent Insights into the Role of B Cells in Chronic Hepatitis B and C Infections

Pathogens, Год журнала: 2023, Номер 12(6), С. 815 - 815

Опубликована: Июнь 8, 2023

Chronic viral hepatitis infections, caused by the B or C virus, are a major global health problem causing an estimated one million deaths each year. Immunological studies have classically focused on T cells, while cells largely been neglected. Emerging evidence, however, highlights role for in immunopathogenesis of chronic and infections. cell responses appear to be altered across different clinical phases HBV infection stages disease HCV infection. These show signs more activated state with simultaneous enrichment phenotypically exhausted atypical memory cells. Despite fact that activating signature infection, antibody HBsAg remain impaired glycoprotein E2-specific neutralizing delayed acute phase At same time, reported subset HBV- HCV-specific exhibit phenotype. This may, at least part, explain why patients suboptimal. Here, we summarize recent findings discuss upcoming research questions looking forward how new single-cell technologies could provide novel insights into

Язык: Английский

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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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Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 18, 2024

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding Chronic (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, pathogenesis. However, dynamic crucial factors involved transition from HBV infection to activation intrahepatic inflammation remain elusive. Recent insights have illuminated HBV’s exploitation sodium taurocholate co-transporting polypeptide (NTCP) manipulation cholesterol transport system shared between macrophages hepatocytes for viral entry. These discoveries deepen our as that hijacks hepatocyte metabolism. Moreover, hepatic niche exhibit significant phenotypic functional diversity, zonal characteristics, play essential roles, either maintaining homeostasis or contributing pathogenesis diseases. Therefore, we underscore recent revelations concerning importance context hepatitis. This review particularly emphasizes role HBV-induced metabolic changes key factor activation, ultimately culminating inflammation. alterations offer promising targets therapeutic interventions serve valuable early warning indicators, shedding light progression.

Язык: Английский

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Oncogenic viruses and host lipid metabolism: a new perspective

Journal of General Virology, Год журнала: 2023, Номер 104(6)

Опубликована: Июнь 6, 2023

As noncellular organisms, viruses do not have their own metabolism and rely on the of host cells to provide energy metabolic substances for life cycles. Increasing evidence suggests that infected with oncogenic dramatically altered requirements produce used viral replication virion production by altering cell metabolism. We focused processes which manipulate lipid disorders occur in virus-associated diseases. A deeper understanding infections cause changes could help development new antiviral agents as well potential therapeutic targets.

Язык: Английский

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