PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus
Ying LiHuihui MaYongjian ZhangTinghui HeBinyang LiH. RenJia FengJie ShengKai LiQian YuYunfeng WangHaoran ZhaoJie HeHuicheng LiHongjin WuYuanfei YaoMing Shi
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Abstract:
Spontaneous clearance of hepatitis B virus (HBV) is frequent in adults (95%) but rare in infants (5%), emphasizing the critical role of age-related hepatic immunocompetence. However, the underlying mechanisms of hepatocyte-specific immunosurveillance and age-dependent HBV clearance remain unclear. Here, we identified PGLYRP2 as a hepatocyte-specific pattern recognition receptor with age-dependent expression, and demonstrated that phase separation of PGLYRP2 was a critical driver of spontaneous HBV clearance in hepatocytes. Mechanistically, PGLYRP2 recognized and potentially eliminated covalently closed circular DNA (cccDNA) via phase separation, coordinated by its intrinsically disordered region and HBV DNA-binding domain (PGLYRP2IDR/209-377) in the nucleus. Additionally, PGLYRP2 suppressed HBV capsid assembly by directly interacting with the viral capsid, mediated by its PGRP domain. This interaction promoted the nucleocytoplasmic translocation of PGLYRP2 and subsequent secretion of the PGLYRP2-HBV capsid complex, thereby bolstering the hepatic antiviral response. Pathogenic variants or deletions in PGLYRP2 impaired its ability to inhibit HBV replication, highlighting its essential role in hepatocyte-intrinsic immunity. These findings suggest that targeting the PGLYRP2-mediated host-virus interaction may offer a potential therapeutic strategy for the development of anti-HBV treatments, representing a promising avenue for achieving a functional cure for HBV infection.Keywords:
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This paper presents a concise history of the Single Euro Payments Area (SEPA), with particular emphasis on its impacts on clearing and settlement practices, and on the role of the European Automated Clearing Association as a forum to support the standardisation, harmonisation and consolidation of European payment systems. The paper provides policymakers, scholars and practitioners with an introductory overview, and will help readers, especially those new to SEPA, to understand both its history and more recent developments in the euro area. The conclusions highlight the indispensable role of clearing and settlement infrastructures as a backbone for the payment services delivered by banks, as well as the importance of collaboration for infrastructural evolution.
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The International Commodities Clearing House (icch) has been providing futures markets in London with clearing and guaranteeing services since its formulation as the London Produce Clearing House Limited in 1888. Sugar and coffee were the first two commodities to use the Company's clearing services after 1888, and the Cocoa trade followed in 1928, with the opening of the London Market.
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This study investigated the impact of automated clearing system on the Nigerian banking system. Secondary data were mostly sourced through The Central Bank of Nigeria publications and analyzed using t test statistics, which tested the significant difference between pre, and post automated clearing system. The result revealed that automated clearing system has a significant positive impact on the general payment system. The paper concludes that the post NACS era is more efficient and hence we recommend the application of the automated clearing system that may further reduce the delivery settlement period from current T3 to To
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Abstract As briefly indicated in Chapters 1 and 9, clearing is a process that takes place after trading and before settlement. Its purpose is to manage the credit exposures that arise during this interval between the parties to a trade. The core function of clearing is the novation of market contracts, whereby a clearing houseis interposed between the original trade counterparties. Trades are novated so that the original contract between the buyer and the seller is replaced by two new contracts, one between seller and the clearing house and buyer, one between the buyer and the clearing house as seller.
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The given article highlights the nature and content of the modern clearing and settlement systems. The key principles of the worldwide
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Key words: clearing, settlement and clearing system, clearing and settlement activities, clearing relationships; clearing organization.
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