细小病毒B19整合入人CD36⁺红系祖细胞。
Parvovirus B19 integration into human CD36+ erythroid progenitor cells.
作者信息
Janovitz Tyler, Wong Susan, Young Neal S, Oliveira Thiago, Falck-Pedersen Erik
机构信息
Tri-Institutional MD-PhD Program, USA; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
出版信息
Virology. 2017 Nov;511:40-48. doi: 10.1016/j.virol.2017.08.011. Epub 2017 Aug 12.
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.
致病性人微小病毒B19（B19V）可有效感染红系祖细胞（EPC）。B19V非结构蛋白（NS1）是一种DNA结合内切酶，与腺相关病毒（AAV）的Rep蛋白在功能上具有相似性，这使我们推测NS1可能有助于对人类基因组进行靶向切口并促进B19病毒DNA整合。我们采用了一种整合捕获测序方案（IC-Seq）来筛选感染B19V的人类CD36 + EPC中的病毒整合体，发现了40,000个分布在整个人类基因组中的独特B19V整合事件。对整合模式的计算分析揭示了与基因内含子区域、H3K9me3位点的强相关性，以及鉴定出具有八核苷酸核心基序的41个碱基对共有序列。该八核苷酸核心与B19V的一个单一区域具有同源性，该区域与P6启动子TATA盒相邻。我们提供了首个直接证据，证明红系祖细胞感染B19V会破坏人类基因组并促进病毒DNA整合。
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