An immunocompetent mouse model revealed that congenital Zika virus infection disrupted hippocampal function by
Wei Yang1, Zhan-Zhan Bian2, Zhe Li1
1National Center of Technology Innovation for animal model, National Human Diseases Animal Model Resource Center, Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS & PUMC, Beijing, People's Republic of China.
Insights
Congenital Zika virus (ZIKV) infection impacts infant brain development, primarily affecting the hippocampus. This study reveals ZIKV disrupts hippocampal function by activating autophagy, offering insights for clinical interventions.
Area of Science:
- Neuroscience
- Developmental Biology
- Virology
Background:
- Congenital Zika virus (ZIKV) infection causes significant neurodevelopmental abnormalities in infants.
- The precise mechanisms underlying ZIKV-induced neurodevelopmental issues remain largely unknown.
- Identifying key affected brain regions is crucial for effective clinical intervention.
Purpose of the Study:
- To investigate the primary brain regions affected by congenital ZIKV infection.
- To elucidate the cellular and molecular mechanisms of ZIKV's impact on neurodevelopment.
- To establish a murine model for studying long-term ZIKV-induced neurodevelopmental effects.
Main Methods:
- Construction of a congenital ZIKV-infected murine model using immunocompetent human STAT2 knock-in mice.
- Longitudinal assessment of neurodevelopmental abnormalities and symptoms.
- Transcriptional and pathological analysis of affected brain tissues, focusing on the hippocampus.
Main Results:
- The hippocampus was identified as the main brain region impacted by congenital ZIKV infection.
- Congenital ZIKV infection led to long-term neurodevelopmental abnormalities and symptoms in the murine model.
- Hippocampal cells exhibited increased susceptibility to autophagy at both transcriptional and pathological levels during the mice's growth period.
Conclusions:
- Congenital ZIKV infection disrupts hippocampal function by activating autophagy.
- These findings provide a theoretical basis for developing clinical treatments for infants with congenital ZIKV infection.
- Understanding ZIKV's impact on hippocampal autophagy is key to addressing neurodevelopmental deficits.
Abstract:
Congenital Zika virus (ZIKV) infection significantly affects neurological development in infants and subsequently induces neurodevelopmental abnormality symptoms; however, the potential mechanism is still unknown. Therefore, in order to effectively intervene in neurodevelopmental abnormalities in infected infants, it is necessary to identify the main brain regions affected by congenital infection. In this study, we constructed a congenital ZIKV-infected murine model using immunocompetent human STAT2 knock-in mice, which presented long-term neurodevelopmental abnormalities with abnormal neurodevelopmental symptoms. We found that the hippocampus, which regulates cognitive behaviour and processes spatial information and navigation, was the main brain region affected by congenital infection and that hippocampal cells were more prone to autophagy during the growth period of these mice at the transcriptional and pathological levels. These findings highlighted that congenital ZIKV infection could interrupt hippocampal function by activating autophagy, thus providing a theoretical basis for the clinical treatment of congenital ZIKV-infected infants.
