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.
Highlights
Human bocavirus 1 (HBoV1) belongs to the Bocaparvovirus genus in the Parvoviridae family [1,2]
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 human primary airway epithelium (HAE)-ALI cultures
We demonstrated that human bocavirus 1 (HBoV1), an autonomous human Bocaparvovirus, replicates its genome in well-differentiated primary human airway epithelial cells
Summary
Human bocavirus 1 (HBoV1) belongs to the Bocaparvovirus genus in the Parvoviridae family [1,2]. HBoV1 is one of a group of etiological respiratory viruses that cause acute respiratory tract infections in young children. Studies of children with pneumonia, acute wheezing, asthma, and/or bronchiolitis suggest that HBoV1 infects the lower respiratory airways down to the bronchioles [3,5]. HBoV1 infects well-differentiated or polarized human primary airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI) [12]. We have demonstrated that HBoV1 infection of HAE-ALI is long-lasting, persistent, and productive, causing a remarkable loss of epithelial integrity [16,17], which is consistent with the prolonged primary shedding events of HBoV1 for up to a year in patients with respiratory illness [18]
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