Cook Lucy B M, Melamed Anat, Demontis Maria Antonietta, Laydon Daniel J, Fox James M, Tosswill Jennifer H C, de Freitas Declan, Price Ashley D, Medcalf James F, Martin Fabiola, Neuberger James M, Bangham Charles R M, Taylor Graham P
Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Department of Biology and Hull York Medical School, Centre for Immunology and Infection, University of York, York, UK.
Retrovirology. 2016 Jan 8;13:3. doi: 10.1186/s12977-015-0236-7.
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.
1型人类嗜T淋巴细胞病毒（HTLV-1）全球约感染1000万人，感染后会导致终身感染。与高病毒前体载量相关的疾病仅在少数患者中出现。在已确立的感染中，HTLV-1通过感染性淋巴细胞的传播和克隆扩增进行复制。关于急性HTLV-1感染知之甚少。本文报告了3名接受来自1名HTLV-1感染供体器官移植的受者在移植后获得感染的早期HTLV-1感染动力学。在每位受者检测到低水平的HTLV-1前病毒后，于暴露后3周对受者使用两种HTLV-1酶抑制剂进行治疗。通过血清学、病毒前体载量定量、HTLV-1 2LTR DNA环以及HTLV-1独特整合位点分析对HTLV-1感染进行连续监测。
移植后16 - 39天首次检测到HTLV-1抗体。在第16 - 23天通过PCR检测到HTLV-1前病毒，到第38 - 45天增加了2 - 3个对数，前病毒加倍时间峰值为1.4天，之后达到稳定状态。前病毒载量的快速扩增与HTLV-1 2LTR DNA环的高频率相关。与已确立的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，初始寡克隆指数较高，这与早期有丝分裂增殖一致。
在通过器官移植感染的受者中，尽管早期进行了抗HTLV-1治疗，但HTLV-1仍迅速传播。在6周内达到了前病毒载量设定点。血清转化没有延迟。独特整合位点分析和HTLV-1 2LTR DNA环表明早期克隆扩增和高感染传播率。
