Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Imunofarmacologia, Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz-Fiocruz, Centro de Pesquisa, Inovação e Vigilância em COVID-19 e Emergências Sanitárias, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2023 Oct 9;118:e230044. doi: 10.1590/0074-02760230044. eCollection 2023.
Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence in various cell types in the brain and for their suggested involvement in neurodevelopment and neurodegenerative diseases. Only recently have the roles of LD in neuroinfections begun to be explored. Recent findings reveal that lipid remodelling and increased LD biogenesis play important roles for Zika virus (ZIKV) replication and pathogenesis in neural cells. Moreover, blocking LD formation by targeting DGAT-1 in vivo inhibited virus replication and inflammation in the brain. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. Here, we review the progress in understanding LD functions in the central nervous system in the context of the host response to Zika infection.
脂滴 (LD) 是进化上保守的富含脂质的细胞器，具有多种细胞和刺激调节蛋白。越来越多的证据表明，细胞内病原体将 LD 作为能量来源、复制部位和免疫逃避机制的一部分加以利用。然而，LD 也可以作为宿主对病原体的免疫和炎症反应的一部分发挥作用。由于 LD 存在于大脑中的各种细胞类型中，并且其在神经发育和神经退行性疾病中的作用也得到了提示，因此人们对其在中枢神经系统中的功能产生了浓厚的兴趣。最近才开始探索 LD 在神经感染中的作用。最近的研究结果表明，脂质重塑和 LD 生物发生的增加对于寨卡病毒 (ZIKV) 在神经细胞中的复制和发病机制起着重要作用。此外，通过在体内靶向 DGAT-1 阻止 LD 形成可抑制大脑中的病毒复制和炎症。因此，靶向脂质代谢和 LD 生物发生可能是抗 ZIKV 治疗开发的潜在策略。在这里，我们回顾了在宿主对寨卡病毒感染的反应背景下，对 LD 在中枢神经系统中的功能的理解进展。
