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Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.
- Subjects :
- Placenta
Immunology
Virus Replication
Zika virus
Mice
Behavioral Neuroscience
Immune system
Downregulation and upregulation
Pregnancy
Animals
Humans
Medicine
Infectivity
biology
Zika Virus Infection
Endocrine and Autonomic Systems
business.industry
GAS6
Suppressor of cytokine signaling 1
Transplacental
Zika Virus
biology.organism_classification
FLAVIVIRUS
Flavivirus
Female
Nervous System Diseases
business
Subjects
Details
- ISSN :
- 08891591
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- Brain, Behavior, and Immunity
- Accession number :
- edsair.doi.dedup.....b2c0348d3150308d85f4cf12941f1fca