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How ZIKV triggers this event in developing neural cells is not well understood at a molecular level and likely requires many contributing factors. ZIKV efficiently infects human neural progenitor cells (hNPCs) and leads to growth arrest of these cells, which are critical for brain development. Here, we demonstrate that infection with ZIKV, but not dengue virus, disrupts the cell cycle of hNPCs by halting DNA replication during S phase and inducing DNA damage. We further show that ZIKV infection activates the ATM\/Chk2 checkpoint but prevents the activation of another checkpoint, the ATR\/Chk1 pathway. These results unravel an intriguing mechanism by which an RNA virus interrupts host DNA replication. 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