Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses...

Area of Science:

• Reproductive biology
• Virology
• Immunology

Background:

• Zika virus (ZIKV) causes congenital anomalies, necessitating understanding of maternal-fetal transmission.
• The placenta is a likely route for vertical ZIKV transmission.
• Early ZIKV transmission events in the maternal decidua remain poorly understood.

Purpose of the Study:

• To investigate ZIKV replication and transmission dynamics within early human maternal-decidual tissues.
• To characterize the innate immune responses of the maternal-fetal interface to ZIKV infection.
• To compare ZIKV's placental pathogenesis with that of human cytomegalovirus (HCMV).

Main Methods:

• Utilized ex vivo 3D organ cultures of first-trimester and midgestation human decidual tissues and chorionic villi.
• Quantified viral load and infectious virus progeny.
• Performed genome-wide transcriptome analysis to assess host responses.
• Conducted parallel infections with ZIKV and HCMV for comparative analysis.

Main Results:

• ZIKV efficiently replicated in first-trimester and midgestation maternal decidual tissues.
• Viral spread was demonstrated by increasing tissue-associated ZIKV load and infectious virus release.
• Fetus-derived chorionic villi showed reduced ZIKV replication with advancing gestational age.
• ZIKV upregulated decidual innate immune responses, distinct from HCMV, inducing apoptosis and cell death rather than immune cell activation.
• ZIKV infection led to distinct placental tissue innate immune responses and damage pathways.

Conclusions:

• The maternal decidua is a likely site for ZIKV transmission to the fetus.
• ZIKV infection elicits unique placental innate immune responses, characterized by apoptosis and cell death.
• This research provides a model for studying early ZIKV transmission and evaluating therapeutic interventions.