The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach
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DOI：
10.1016/j.celrep.2019.09.016
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发表时间：
2019-10-15
期刊：
影响因子：
8.8
通讯作者：
Satou, Yorifumi
中科院分区：
文献类型：
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作者：
Katsuya, Hiroo;Islam, Saiful;Satou, Yorifumi
逆转录病毒人类T细胞白血病病毒1型（HTLV-1）整合到宿主DNA中，实现持续感染，并诱发人类疾病。在这里，我们证明了病毒DNA捕获测序（DNA捕获-seq）是有用的表征HTLV-1前病毒在自然病毒感染的个人，提供全面的信息，前病毒的结构和病毒的整合位点。我们分析了98名自然HTLV-1感染者的外周血，发现缺陷前病毒不仅存在于白血病患者中，也存在于其他临床实体患者中。我们进一步证明，与缺陷型前病毒的克隆表现出更高程度的克隆丰度比那些全长前病毒。缺陷型前病毒在HTLV-1感染的人源化小鼠中的频率低于感染个体，表明缺陷型前病毒在感染的初始阶段是罕见的，但在持续感染期间优先选择。这些结果证明了病毒DNA-captureseq对HTLV-1感染的鲁棒性，并提示了对人类其他病毒相关癌症的潜在应用。
The retrovirus human T-cell leukemia virus type 1 (HTLV-1) integrates into the host DNA, achieves persistent infection, and induces human diseases. Here, we demonstrate that viral DNA-capture sequencing (DNA-capture-seq) is useful to characterize HTLV-1 proviruses in naturally virus-infected individuals, providing comprehensive information about the proviral structure and the viral integration site. We analyzed peripheral blood from 98 naturally HTLV-1-infected individuals and found that defective proviruses were present not only in patients with leukemia, but also in those with other clinical entities. We further demonstrated that clones with defective-type proviruses exhibited a higher degree of clonal abundance than those with full-length proviruses. The frequency of defective-type proviruses in HTLV-1-infected humanized mice was lower than that in infected individuals, indicating that defective proviruses were rare at the initial phase of infection but preferentially selected during persistent infection. These results demonstrate the robustness of viral DNA-captureseq for HTLV-1 infection and suggest potential applications for other virus-associated cancers in humans.