Question

Question 1: Summarize the effects of the Zika virus (ZIKV) on human neural progenitor cells (hNPCs)

Question 2: How would ZIKV infection of immature neurons possibly lead to the observed microcephaly?

Question 3: How do you think the timing of infection (when a pregnant woman became infected by Zika) might impact the severity of the microcephaly?

Answer 1

Question 1:

• ZIKV preferentially infects and triggers apoptosis in neural progenitor cells
• Inhibition of neuroprogenitor cell differentiation by affecting the NOTCH pathway
• Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells. Further modification of the viral-induced TLR3-mediated immune network in the infected hNPCs affects viral replication.
• Infection of cranial neural crest cells may result in the production of inflammatory cytokines that act in a paracrine manner to deplete neural progenitor cell pools by promoting their apoptosis

• Gene expression changes in hNPCs exposed to ZIKV are associated with the cell cycle, neural migration, differentiation and DNA replication and repair and results in immature differentiation of hNPCs.

Question 2:

• ZIKV infection of immature neurons lead to depletion of proliferating cells in the stem cell compartment of the ventricular zone as well as disruption of corticospinal pyramidal neurons
• Downregulation of neurogenesis and upregulation of apoptosis in hNPCs leads to cell cycle arrest and death of the developing neurons

• ZIKV resulted in cortical infection and thinning, inhibition of neuroprogenitor cell differentiation, and microcephaly

• To summerise, microcephaly is a result of premature differention of developing neurons and their progressive cell death.

Question 3:

• 1st trimester infections are more severe because the neural development is starting at that stage.
• ZIKV exposure towards the early stage of pregnancy causes more devastating effect than infection occuring towards the end stage of pregnancy