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

PLoS Pathogens
Xuefeng DengJianming Qiu

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...Continue Reading

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Citations

Jul 1, 2017·Journal of Virology·Zekun WangJianming Qiu
Nov 4, 2016·Clinical Microbiology Reviews·Jianming QiuNeal S Young
Jul 10, 2019·Annual Review of Virology·Maria Söderlund-Venermo
Sep 15, 2019·Archives of Virology·Vanessa VerbekeElizaveta Padalko
Jun 2, 2020·Journal of Medical Virology·Xuefeng Liu, Abdul M Mondal
Jul 9, 2020·Current Protocols in Microbiology·Ziying YanJianming Qiu
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Apr 9, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julia Fakhiri, Dirk Grimm
Jul 6, 2021·Frontiers in Microbiology·Liting ShaoJianming Qiu
Jun 9, 2021·Equine Veterinary Journal·Anna Sophie RamsauerJessika-M V Cavalleri
Aug 11, 2021·Viruses·Salla MattolaMaija Vihinen-Ranta
Aug 5, 2021·Journal of Virology·Weiran ShenJianming Qiu

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Methods Mentioned

BETA
confocal microscopy
proximity ligation assay
PCR
electrophoresis
Assay

Software Mentioned

ImageQuant TL
Nikon EZ - C1
Multi Gauge

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