Human Bocavirus 1 Is a Novel Helper for Adeno-associated Virus Replication

作者：Zekun Wang, Xuefeng Deng, Wei Zou, John F. Engelhardt, Ziying Yan, Jianming Qiu · 发表于：Journal of Virology · 年份：2017 · DOI：10.1128/jvi.00710-17 · 被引用次数：37 · 研究领域：Respiratory viral infections research、Parvovirus B19 Infection Studies、Virus-based gene therapy research

ABSTRACT Human bocavirus 1 (HBoV1) is an autonomous parvovirus that infects well-differentiated primary human airway epithelia (HAE) in vitro . In human embryonic kidney HEK293 cells, the transfection of a duplex HBoV1 genome initiates viral DNA replication and produces progeny virions that are infectious in HAE. HBoV1 takes advantage of signaling pathways in the DNA damage response for efficient genome amplification in both well-differentiated (nondividing) HAE and dividing HEK293 cells. On the other hand, adeno-associated virus 2 (AAV2) is a helper-dependent dependoparvovirus, and productive AAV2 replication requires coinfection with a helper virus (e.g., adenovirus or herpesvirus) or treatment with genotoxic agents. Here, we report that HBoV1 is a novel helper virus for AAV2 replication. Coinfection by HBoV1 and AAV2 rescued AAV2 replication in HAE cells. The helper function of HBoV1 for AAV2 is not limited to HAE cells but also includes HEK293 and HeLa cells. Importantly, the helper function of HBoV1 for AAV2 relies on neither HBoV1 replication nor the DNA damage response. Following transfection of HEK293 cells, the minimal requirements for the replication of the AAV2 duplex DNA genome and the production of progeny virions included the HBoV1 NP1 and NS4 proteins and a newly identified viral long noncoding RNA (BocaSR). However, following infection of HEK293 and HeLa cells with AAV2 virions, HBoV1 NS2 (but not NS4), NP1, and BocaSR were required for AAV2 DNA replication an...