Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways

Xuefeng Deng; Ziying Yan; Fang Cheng; John F Engelhardt; Jianming Qiu

doi:10.1371/journal.ppat.1005399

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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

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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

Xuefeng Deng, Ziying Yan, Fang Cheng, John F Engelhardt and Jianming Qiu

PLoS pathogens, Vol.12(1), pp.e1005399-e1005399

01/2016

DOI: 10.1371/journal.ppat.1005399

PMCID: PMC4713420

PMID: 26765330

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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.

Human bocavirus - physiology

Parvoviridae Infections - virology

DNA Damage - physiology

Humans

Cells, Cultured

DNA Repair - physiology

Fluorescent Antibody Technique

Immunoblotting

Respiratory Mucosa - virology

Virus Replication - physiology

Details

Title: Subtitle: Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways
Creators: Xuefeng Deng - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America
Ziying Yan - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Fang Cheng - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America
John F Engelhardt - Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
Jianming Qiu - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America
Resource Type: Journal article
Publication Details: PLoS pathogens, Vol.12(1), pp.e1005399-e1005399
DOI: 10.1371/journal.ppat.1005399
PMID: 26765330
PMCID: PMC4713420
NLM abbreviation: PLoS Pathog
ISSN: 1553-7366
eISSN: 1553-7374
Publisher: Public Library of Science; United States
Grant note: AI070723 / NIAID NIH HHS R56 AI070723 / NIAID NIH HHS R21 AI112803 / NIAID NIH HHS AI105543 / NIAID NIH HHS P30 GM103326 / NIGMS NIH HHS R21 AI105543 / NIAID NIH HHS R01 AI070723 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 01/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984025418902771

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