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Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation
Fok-Moon Lum1, Donovan K S Low1, Yiping Fan2
1Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR).
Background:
The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive.
Methods:
Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays.
Results:
We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1).
Conclusions:
Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.
Insights
Zika virus (ZIKV) infects microglia, a key brain immune cell, and triggers inflammation. This finding is crucial for understanding congenital ZIKV disease and its impact on fetal brain development.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Zika virus (ZIKV) reemergence linked to increased microcephaly.
- ZIKV can infect neural progenitors, potentially impairing brain growth.
- Direct evidence of ZIKV in human fetal brain tissue was lacking.
Purpose of the Study:
- To investigate ZIKV infection in human fetal brain cells.
- To identify specific cell types targeted by ZIKV.
- To analyze the inflammatory response induced by ZIKV infection.
Main Methods:
- Analysis of brain cell preparations from 9 donors.
- Flow cytometry to detect ZIKV antigen and cell surface markers.
- Viral RNA quantification to assess replication.
- Immunoassays to measure cytokine levels in infected cells.
Main Results:
- ZIKV infection was prominent in hematopoietic cells, especially microglia.
- Microglia, the brain's resident macrophages, were a primary target.
- Infection elevated proinflammatory mediators like IL-6, TNF-α, IL-1β, and MCP-1.
Conclusions:
- Microglia play a significant role in ZIKV pathogenesis.
- Neuroinflammation is a key factor in congenital ZIKV disease.
- Findings provide insight into ZIKV's impact on fetal brain development.