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

Authors :
Lai M
La Rocca V
Iacono E
Filipponi C
De Carli A
Favaro D
Fonnesu R
Filippini F
Spezia PG
Amato R
Catelli E
Matteo B
Lottini G
Onorati M
Clementi N
Freer G
Piomelli D
Pistello M
Source :
Antiviral research [Antiviral Res] 2023 Aug; Vol. 216, pp. 105664. Date of Electronic Publication: 2023 Jul 04.
Publication Year :
2023

Abstract

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 β-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-α (PPAR-α), directing β-oxidation and preventing inflammation. Our findings indicate that inhibiting NAAA through gene-editing or drugs moderately reduces ZIKV replication by approximately one log <subscript>10</subscript> 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-9096
Volume :
216
Database :
MEDLINE
Journal :
Antiviral research
Publication Type :
Academic Journal
Accession number :
37414288
Full Text :
https://doi.org/10.1016/j.antiviral.2023.105664