title: Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways.
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.
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: Engelhardt
authors.affiliation: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
mesh_terms: D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D005455:Fluorescent Antibody Technique; D056661:Human bocavirus / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D010322:Parvoviridae Infections / Q000821:virology*; D020545:Respiratory Mucosa / Q000821:virology*; D014779:Virus Replication / Q000502:physiology*