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解锁秘密:脂质代谢和脂滴在 SARS-CoV-2 感染和免疫反应中的关键作用。

Unlocking secrets: lipid metabolism and lipid droplet crucial roles in SARS-CoV-2 infection and the immune response.

机构信息

Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation, Fiocruz, Brasil Ave, Rio de Janeiro, RJ, 21040-361, Brazil.

Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies, Oswaldo Cruz Foundation, Fiocruz, Brasil Ave, Rio de Janeiro, RJ, 21040-361, Brazil.

出版信息

J Leukoc Biol. 2024 Nov 27;116(6):1254-1268. doi: 10.1093/jleuko/qiae170.

DOI:10.1093/jleuko/qiae170
PMID:39087951
Abstract

Lipid droplets (LDs) are crucial for maintaining lipid and energy homeostasis within cells. LDs are highly dynamic organelles that present a phospholipid monolayer rich in neutral lipids. Additionally, LDs are associated with structural and nonstructural proteins, rapidly mobilizing lipids for various biological processes. Lipids play a pivotal role during viral infection, participating during viral membrane fusion, viral replication, and assembly, endocytosis, and exocytosis. SARS-CoV-2 infection often induces LD accumulation, which is used as a source of energy for the replicative process. These findings suggest that LDs are a hallmark of viral infection, including SARS-CoV-2 infection. Moreover, LDs participate in the inflammatory process and cell signaling, activating pathways related to innate immunity and cell death. Accumulating evidence demonstrates that LD induction by SARS-CoV-2 is a highly coordinated process, aiding replication and evading the immune system, and may contribute to the different cell death process observed in various studies. Nevertheless, recent research in the field of LDs suggests these organelles according to the pathogen and infection conditions may also play roles in immune and inflammatory responses, protecting the host against viral infection. Understanding how SARS-CoV-2 influences LD biogenesis is crucial for developing novel drugs or repurposing existing ones. By targeting host lipid metabolic pathways exploited by the virus, it is possible to impact viral replication and inflammatory responses. This review seeks to discuss and analyze the role of LDs during SARS-CoV-2 infection, specifically emphasizing their involvement in viral replication and the inflammatory response.

摘要

脂滴 (LDs) 对于维持细胞内的脂质和能量稳态至关重要。LDs 是高度动态的细胞器,具有富含中性脂质的磷脂单层。此外,LDs 与结构和非结构蛋白相关联,可快速为各种生物过程动员脂质。脂质在病毒感染过程中起着关键作用,参与病毒膜融合、病毒复制和组装、内吞作用和外排作用。SARS-CoV-2 感染常诱导 LD 积累,其被用作复制过程的能量来源。这些发现表明,LDs 是病毒感染的标志,包括 SARS-CoV-2 感染。此外,LDs 参与炎症过程和细胞信号转导,激活与先天免疫和细胞死亡相关的途径。越来越多的证据表明,SARS-CoV-2 诱导的 LD 诱导是一个高度协调的过程,有助于复制并逃避免疫系统,并且可能导致在不同研究中观察到的不同细胞死亡过程。然而,最近关于 LDs 的研究表明,根据病原体和感染条件,这些细胞器也可能在免疫和炎症反应中发挥作用,保护宿主免受病毒感染。了解 SARS-CoV-2 如何影响 LD 的生物发生对于开发新药物或重新利用现有药物至关重要。通过靶向宿主被病毒利用的脂质代谢途径,有可能影响病毒复制和炎症反应。本综述旨在讨论和分析 LDs 在 SARS-CoV-2 感染期间的作用,特别强调其在病毒复制和炎症反应中的参与。

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