Inapparent maternal ZIKV infection impacts fetal brain development and postnatal behavior

Area of Science:

• Neuroscience
• Virology
• Developmental Biology

Background:

• Zika virus (ZIKV) is linked to severe infant neurological issues like microcephaly and congenital Zika syndrome (CZS).
• The long-term neurological effects of mild or inapparent maternal ZIKV infections are not well understood.

Purpose of the Study:

• To investigate the impact of mid-gestation maternal ZIKV infection on fetal neurodevelopment using a human STAT2 knock-in mouse model.
• To identify molecular and behavioral changes in offspring following asymptomatic maternal ZIKV exposure.

Main Methods:

• Maternal ZIKV infection in hSTAT2 mice during mid-gestation.
• Transcriptomic analysis of fetal brain tissue.
• Synaptic density assessment in the hippocampus.
• Chemically induced seizure susceptibility testing.
• Unsupervised machine learning analysis of spontaneous behavior using motion sequencing (MoSeq).

Main Results:

• Maternal ZIKV infection resulted in vertical transmission without overt clinical signs in dams or offspring.
• Significant alterations in fetal brain gene expression related to synaptic function and neuronal development were observed.
• Offspring exhibited increased hippocampal synaptic density and heightened seizure susceptibility.
• Persistent, sex-biased alterations in spontaneous motor behavior were detected in offspring.

Conclusions:

• Mild maternal ZIKV infections can lead to subtle but significant long-term neurological consequences in offspring.
• These findings underscore the importance of monitoring children exposed to ZIKV in utero, even without severe birth outcomes.
• The study provides a valuable model and datasets for further research into inapparent maternal ZIKV infection impacts.