How Zika virus attacks the developing human brain

How Zika virus attacks the developing human brain
 

Congenital Zika virus (ZIKV) infection has been tied to birth defects, such as microcephaly, but the virus’ mechanism of action and precise target cells in the fetal brain remain unclear.
 
Using primary human brain cortical tissue cultures, researchers found that in the second-trimester fetal brain ZIKV targets neural stem cells, astrocytes, oligodendrocyte progenitors, and microglia, while largely sparing neurons.
 
Infection of astrocytes late in fetal brain development might explain the clinical reports of calcified bands observed in the brain’s cortical plate among newborn children with congenital ZIKV infection. Blocking a putative viral entry factor called the AXL receptor using antibodies and CRISPR interference suggested that the extracellular domain of the receptor, which likely serves as a viral handhold, is critical for glial cell infection.
 
Further, the authors screened more than 2,100 FDA-approved chemical compounds, including drugs considered safe for use during pregnancy, and found that the macrolide antibiotic azithromycin (AZT), currently prescribed for treating sexually transmitted infections in pregnant women, reduced viral replication and virus-induced damage in cultured human glial cells.
 
AZT outperformed daptomycin, known for its anti- ZIKV activity in cultured cells, in lowering the infection rate of cultured glial cells. According to the authors, the findings offer a fulcrum for the development of therapeutic strategies against congenital ZIKV infection.
 

http://www.pnas.org/content/early/2016/11/28/1618029113

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