4.7 Article

Inhibiting immunoregulatory amidase NAAA blocks ZIKV maturation in Human Neural Stem Cells

期刊

ANTIVIRAL RESEARCH
卷 216, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.antiviral.2023.105664

关键词

PEA; NAAA; Inflammation; Antiviral drugs; ZIKV; ss(+)RNA viruses

向作者/读者索取更多资源

Recent evidence suggests that lipids play a crucial role in viral infections by altering host lipids and interfering with lipogenesis. In the case of Zika virus (ZIKV), inhibiting N-Acylethanolamine acid amidase (NAAA) reduces viral replication and blocks virus maturation. This study highlights NAAA as a potential target for combating ZIKV infection.
Recent evidence suggests that lipids play a crucial role in viral infections beyond their traditional functions of supplying envelope and energy, and creating protected niches for viral replication. In the case of Zika virus (ZIKV), it alters host lipids by enhancing lipogenesis and suppressing & beta;-oxidation to generate viral factories at the endoplasmic reticulum (ER) interface. This discovery prompted us to hypothesize that interference with lipogenesis could serve as a dual antiviral and anti-inflammatory strategy to combat the replication of positive sense single-stranded RNA (ssRNA+) viruses.To test this hypothesis, we examined the impact of inhibiting N-Acylethanolamine acid amidase (NAAA) on ZIKV-infected human Neural Stem Cells. NAAA is responsible for the hydrolysis of palmitoylethanolamide (PEA) in lysosomes and endolysosomes. Inhibition of NAAA results in PEA accumulation, which activates peroxisome proliferator-activated receptor-& alpha; (PPAR-& alpha;), directing & beta;-oxidation and preventing inflammation.Our findings indicate that inhibiting NAAA through gene-editing or drugs moderately reduces ZIKV replication by approximately one log10 in Human Neural Stem Cells, while also releasing immature virions that have lost their infectivity. This inhibition impairs furin-mediated prM cleavage, ultimately blocking ZIKV maturation. In summary, our study highlights NAAA as a host target for ZIKV infection.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据