In-depth characterization of congenital Zika syndrome in immunocompetent mice: antibody-dependent enhancement and an antiviral peptide therapy
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2019
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Background: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including micro cephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome.
Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocom petent mice.
Methods: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a
sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody dependent enhancement phenomenon (ADE) during short and long outcomes of CZI.
Findings: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of
foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of
pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a
decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption
in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody.
Interpretation: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompe tent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral
treatment with AH-D peptide may be beneficial during early maternal ZIKV infection.
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Congenital Zika virus infection (CZI), Congenital Zika Syndrome (CZS), Maternal Immune Activation (MIA), Antibody-Dependent Enhancement (ADE), Short and long-term outcomes
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CAMARGOS, Vidyleison N. et al. In-depth characterization of congenital Zika syndrome in immunocompetent mice: antibody-dependent enhancement and an antiviral peptide therapy. eBiomedicine, Amsterdam, v. 44, p. 516-529, 2019. DOI: 10.1016/j.ebiom.2019.05.014. Disponível em: https://www.sciencedirect.com/science/article/pii/S2352396419303159?via%3Dihub. Acesso em: 20 mar. 2025.