The Large Nonstructural Protein (NS1) of Human Bocavirus 1 Directly Interacts with Ku70, Which Plays an Important Role in Virus Replication in Human Airway Epithelia

• DOI: 10.1128/jvi.01840-21
• Publication Date: 2021-12-08T19:15:35Z
• Authors: Liting Shao; Kang Ning; Jianke Wang; Fang Cheng; Shengqi Wang; Jianming Qiu
• Keywords: Human bocavirus; Ku70

Human bocavirus 1 (HBoV1), an autonomous human parvovirus, causes acute respiratory tract infections in young children. HBoV1 infects well-differentiated (polarized) airway epithelium cultured at air-liquid interface (HAE-ALI). expresses a large nonstructural protein, NS1, that is essential for viral DNA replication. infection of polarized epithelial cells induces damage response (DDR) critical to replication involving repair with error-free Y-family polymerases. NS1 or the isoform NS1-70 per se DDR. In this study, using second-generation proximity-dependent biotin identification (BioID2) approach, we identified Ku70 associated NS1-BioID2 pulldown complex through direct interaction NS1. Biolayer interferometry (BLI) assay determined high binding affinity Ku70, which has equilibrium dissociation constant (KD) value 0.16 μM and processes strongest C-terminal domain. The association was also revealed during HAE-ALI. Knockdown overexpression domain significantly decreased Thus, our study provides, first time, parvovirus protein Ku70. IMPORTANCE Parvovirus plays pivotal role DDR includes activation ATM (ataxia telangiectasia mutated), ATR (ATM- RAD3-related), DNA-PKcs (DNA-dependent kinase catalytic subunit). (NS1) often induction DDR; however, how induced simply by not well studied. Activation been shown as one key pathways HBoV1. We directly interacts but Ku80, Ku70/Ku80 heterodimer affinity. This important propose recruits center, activates facilitates