Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.
Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.
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DOI：
10.1186/s12977-015-0236-7
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发表时间：
2016-01-08
期刊：
影响因子：
3.3
通讯作者：
Taylor GP
中科院分区：
文献类型：
--
作者：
Cook LB;Melamed A;Demontis MA;Laydon DJ;Fox JM;Tosswill JH;de Freitas D;Price AD;Medcalf JF;Martin F;Neuberger JM;Bangham CR;Taylor GP
人类嗜T淋巴细胞病毒1型（HTLV-1）感染全球约1 000万人，传播导致终身感染。与高前病毒负荷相关的疾病发生在少数人中。在已建立的感染中，HTLV-1通过感染性传播和受感染淋巴细胞的克隆扩增进行复制。对急性HTLV-1感染知之甚少。本文报道了来自一个HTLV-1感染供体的三个受者在移植获得性感染后早期HTLV-1感染的动力学。暴露后3周，在每个受体中检测到低水平的HTLV-1前病毒后，用两种HTLV-1酶抑制剂治疗受体。通过血清学、前病毒载量和HTLV-1 2LTR DNA环的定量以及通过HTLV-1独特整合位点分析连续监测HTLV-1感染。移植后16-39天首次检测到HTLV-1抗体。在第16- 2 - 3天通过PCR检测到HTLV-1前病毒，到第38-45天增加2-3 log，峰值前病毒倍增时间为1.4天，之后达到稳态。前病毒载量的快速扩增与高频率的HTLV-1 2LTR DNA环相关。与已建立的HTLV-1感染相比，HTLV-1独特整合位点的数量较高。早在第37天就检测到感染细胞的克隆扩增，具有高的初始寡克隆性指数，与早期有丝分裂增殖一致。在通过器官移植感染的受者中，尽管早期抗HTLV-1治疗，HTLV-1仍迅速传播。在6周内达到前病毒载量设定点。血清转化未延迟。独特的整合位点分析和HTLV-1 2LTR DNA环表明早期克隆扩增和高感染传播率。
Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis. HTLV-1 antibodies were first detected 16–39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16–23 and increased by 2–3 log by day 38–45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation. In recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early anti-HTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread.