Zika Virus Infection Induces DNA Damage Response in Human Neural Progenitors That Enhances Viral Replication

Journal of Virology
Christy HammackHengli Tang

Abstract

Zika virus (ZIKV) infection attenuates the growth of human neural progenitor cells (hNPCs). As these hNPCs generate the cortical neurons during early brain development, the ZIKV-mediated growth retardation potentially contributes to the neurodevelopmental defects of the congenital Zika syndrome. Here, we investigate the mechanism by which ZIKV manipulates the cell cycle in hNPCs and the functional consequence of cell cycle perturbation on the replication of ZIKV and related flaviviruses. We demonstrate that ZIKV, but not dengue virus (DENV), induces DNA double-strand breaks (DSBs), triggering the DNA damage response through the ATM/Chk2 signaling pathway while suppressing the ATR/Chk1 signaling pathway. Furthermore, ZIKV infection impedes the progression of cells through S phase, thereby preventing the completion of host DNA replication. Recapitulation of the S-phase arrest state with inhibitors led to an increase in ZIKV replication, but not of West Nile virus or DENV. Our data identify ZIKV's ability to induce DSBs and suppress host DNA replication, which results in a cellular environment favorable for its replication.IMPORTANCE Clinically, Zika virus (ZIKV) infection can lead to developmental defects in the cortex of the fet...Continue Reading

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Citations

Jun 13, 2020·Global Pediatric Health·Harbir Singh Arora
Mar 3, 2020·Frontiers in Immunology·Franciane Mouradian Emidio TeixeiraMaria Notomi Sato
Sep 25, 2019·Viruses·Pietro ScaturroAndreas Pichlmair
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Viviane Souza de CamposDaniel Adesse
Aug 5, 2021·PLoS Neglected Tropical Diseases·Li-Min XieXu-Guang Guo
Oct 28, 2021·Proteomics. Clinical Applications·Mauricio Quiñones-VegaGilberto B Domont

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