Inflammation Exacerbates Congenital Zika Virus Infection and Naringenin Provides Protective Effects

Area of Science:

• Virology
• Immunology
• Developmental Biology

Background:

• Congenital Zika Syndrome (CZS) arises from maternal Zika virus (ZIKV) infection during pregnancy.
• Pathogenesis mechanisms at the placental barrier are not fully understood.
• Understanding ZIKV placental pathology is crucial for preventing fetal complications.

Purpose of the Study:

• To investigate ZIKV infection mechanisms in the placenta.
• To evaluate the role of placental inflammation in ZIKV pathogenesis.
• To explore Naringenin (NGN) as a potential therapeutic agent.

Main Methods:

• Combined clinical placental analysis, placental explant cultures, and a murine model.
• Histopathological and immunohistochemical analyses of human placentas.
• In vitro inflammation models and in vivo NGN treatment studies.

Main Results:

• ZIKV-infected placentas from CZS newborns showed increased inflammation (Hofbauer cell hyperplasia, villitis, decidual inflammation).
• Reduced TLR4 expression and altered cytokine levels (TNF, IL-10) were observed in CZS placentas.
• Inflammation exacerbated ZIKV replication; NGN treatment rescued inflammatory and virological outcomes in vitro and alleviated microcephaly in vivo.

Conclusions:

• Placental inflammation is a key factor in ZIKV replication and fetal brain malformation.
• Naringenin (NGN) demonstrates bifunctional antiviral and anti-inflammatory properties.
• NGN is a potential therapeutic candidate for mitigating ZIKV developmental impacts.