Zika virus cell tropism in the developing human brain and inhibition by azithromycin

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Abstract
Significance: Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly spread through the Americas and has been associated with fetal abnormalities, including microcephaly. To understand how microcephaly develops, it is important to identify which cell types of the developing brain are susceptible to infection. We use primary human tissue to show that radial glia and astrocytes are more susceptible to infection than neurons, a pattern that correlates with expression of a putative viral entry receptor, AXL. We also perform a screen of Food and Drug Administration-approved compounds, with an emphasis on drugs known to be safe in pregnancy. We identify an antibiotic, azithromycin, that reduces viral proliferation in glial cells, and compare its activity with daptomycin and sofosbuvir, two additional drugs with anti-ZIKV activity.
Funding Information
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (R01NS075998)
  • HHS | NIH | National Institute of Neurological Disorders and Stroke (U01 MH105989)
  • Howard Hughes Medical Institute (n/a)
  • HHS | NIH | National Institute of Mental Health (R01MH099595-01)
  • Paul G. Allen Family Foundation (n/a)
  • Damon Runyon Cancer Research Foundation (n/a)