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

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. © 2016 deng et al.