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#Zika virus

2 public questions tagged with this topic.

Teratogens

Zika alters brain size through changes in:

Zika virus neuropathogenesis involves manipulation of host noncoding RNA regulation beyond protein targeting. In neural progenitors infection dysregulates microRNA biogenesis, altering levels of brain-enriched miRNAs such as miR-9, miR-124, let-7 family and miR-132 that control cell cycle, differentiation timing and apoptosis. Subgenomic flavivirus RNAs sequester Dicer and Ago proteins impairing processing. Changes in microRNA profiles lead to premature cell cycle exit, increased caspase activation and reduced proliferation of cortical progenitors. DNA methylation or phosphorylation alterations less central. Consequently brain growth reduction after Zika reflects altered microRNA levels governing neurogenesis and cortical expansion.

Ref: Nature Cell Biology: Zika alters brain size via microRNA changes.

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Teratogens

Zika virus causes microcephaly by infecting:

Zika virus microcephaly pathogenesis involves selective infection of embryonic neuroepithelium. Flavivirus crosses placenta via trophoblast and infects radial glial progenitors expressing AXL receptor in ventricular zone. Viral nonstructural proteins NS4A and NS4B inhibit Akt-mTOR signaling, induce endoplasmic reticulum stress, cell cycle arrest and apoptosis, depleting stem pool. Additionally virus dysregulates host microRNAs and centrosomal proteins, causing premature differentiation. Adult neurons possess interferon responses limiting replication. Preferential targeting of cycling neural progenitor cells explains cortex-specific thinning and severe brain size reduction observed after gestational infection.

Ref: Nature Reviews Neuroscience: Zika virus infection of neural progenitors microcephaly mechanism.

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