EVs Containing Host Restriction Factor IFITM3 Inhibited ZIKV Infection of Fetuses in Pregnant Mice through Trans-placenta Delivery.
Mol Ther
; 29(1): 176-190, 2021 01 06.
Article
em En
| MEDLINE
| ID: mdl-33002418
ABSTRACT
Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interações Hospedeiro-Patógeno
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Resistência à Doença
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Vesículas Extracelulares
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Zika virus
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Infecção por Zika virus
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Proteínas de Membrana
Tipo de estudo:
Guideline
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Prognostic_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China