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Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways
Deng, Xuefeng Yan, Ziying Cheng, Fang Engelhardt, John F. Qiu, Jianming
Deng, Xuefeng
Yan, Ziying
Cheng, Fang
Engelhardt, John F.
Qiu, Jianming
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Abstract
Human bocavirus 1 (HBoV1) belongs to the genus Bocaparvovirus of the Parvoviridae family, and is an emerging human pathogenic respiratory virus. In vitro, HBoV1 infects well-differentiated/polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). Although it is well known that autonomous parvovirus replication depends on the S phase of the host cells, we demonstrate here that the HBoV1 genome amplifies efficiently in mitotically quiescent airway epithelial cells of HAE-ALI cultures. Analysis of HBoV1 DNA in infected HAE-ALI revealed that HBoV1 amplifies its ssDNA genome following a typical parvovirus rolling-hairpin DNA replication mechanism. Notably, HBoV1 infection of HAE-ALI initiates a DNA damage response (DDR) with activation of all three phosphatidylinositol 3-kinase–related kinases (PI3KKs). We found that the activation of the three PI3KKs is required for HBoV1 genome amplification; and, more importantly, we identified that two Y-family DNA polymerases, Pol η and Pol κ, are involved in HBoV1 genome amplification. Overall, we have provided an example of de novo DNA synthesis (genome amplification) of an autonomous parvovirus in non-dividing cells, which is dependent on the cellular DNA damage and repair pathways.
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Date
2016-01-14
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Public Library of Science
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Keywords
DNA replication, Epithelial cells, DNA repair, Viral replication, Phosphorylation, DNA polymerase, Membrane staining, Cell differentiation
Citation
Deng, Xuefeng, Ziying Yan, Fang Cheng, John F. Engelhardt, and Jianming Qiu. "Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways." PLoS Pathog PLOS Pathogens 12.1 (2016): n. pag. doi:10.1371/journal.ppat.1005399