β-Catenin Restricts Zika Virus Internalization by Downregulating Axl

Area of Science:

• Neuroscience
• Virology
• Cell Biology

Background:

• The Zika virus (ZIKV) outbreak in the Americas caused severe neurological issues, notably microcephaly.
• Astrocytes are crucial for maintaining brain homeostasis and are implicated in ZIKV pathogenesis.

Purpose of the Study:

• To investigate the mechanisms governing ZIKV entry into human fetal astrocytes (HFAs).
• To elucidate the role of beta-catenin and Axl in ZIKV infection of brain cells.

Main Methods:

• Transcriptional regulation analysis of Axl by beta-catenin in HFAs.
• Assessment of ZIKV entry and replication in astrocytes and other cell types.
• Comparison of ZIKV strains with different genetic backgrounds.

Main Results:

• Beta-catenin transcriptionally downregulates Axl, a key receptor for ZIKV entry into HFAs.
• ZIKV actively inhibits beta-catenin to upregulate Axl and facilitate its own internalization.
• This interaction is specific to brain cells like astrocytes and microvascular cells, not kidney cells.

Conclusions:

• Beta-catenin plays a critical role in restricting ZIKV entry into astrocytes.
• ZIKV employs a strategy to downregulate beta-catenin, thereby enhancing its own entry via Axl.
• This highlights a complex host-pathogen interaction crucial for ZIKV neuropathogenesis.