The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration.

病原性自主人类细小病毒B19（B19V）生产性感染红系祖细胞（EPC）。B19V非结构蛋白（NS1），DNA结合核酸内切酶和腺相关病毒（AAV）的Rep蛋白之间的功能相似性使我们假设NS1可能促进人类基因组的靶向切口和B19 vDNA整合。我们采用了整合捕获测序协议（IC-Seq）来筛选B19V感染的人CD36 + EPC中的病毒整合剂，并发现了分布在整个人类基因组中的40,000个独特的B19V整合事件。整合模式的计算分析显示与基因内含子区域，H3K9me3位点，以及与一个八核苷酸核心基序的41个碱基对的共有序列的确定密切相关。八核苷酸核心与邻近P6启动子TATA盒的B19V单个区域具有同源性。我们提出的第一个直接证据表明，类红细胞祖细胞的B19V感染破坏了人类基因组并促进了病毒DNA的整合。