Human bocavirus NP1 antagonizes host type I interferon response through repressing the nuclear transport of STAT1.

Human bocavirus 1 (HBoV1), first identified in human nasopharyngeal specimens in 2005, is a relatively recent member of the respiratory virus family and is primarily associated with respiratory tract infections. Despite this, the mechanisms underlying HBoV1 pathogenesis remain poorly understood, primarily due to the lack of suitable cell lines and animal models, as well as the complicating factor of co-infections with other pathogens. In this study, we demonstrate that the non-structural protein 1 (NP1) of HBoV1 antagonizes the type I interferon (IFN-I) signaling pathway. NP1 interacts with the DNA-binding domain (DBD) of signal transducer and activator of transcription 1 (STAT1) and the importing β-binding (IBB) domain of karyopherin subunit alpha-1 (KPNA1), thereby disrupting the formation of the STAT1/KPNA1/KPNB1 complex and subsequently inhibiting STAT1 nuclear translocation, a critical step in IFN-I signaling. Furthermore, we show that HBoV1 NP1 facilitates the replication of influenza A virus (IAV) and respiratory syncytial virus (RSV). These findings suggest a novel mechanism by which bocavirus proteins antagonize the host's innate immune response and provide new evidence that bocavirus may exacerbate the symptoms of clinical respiratory viral infections.