Zhao Tong-Mao, Hague Bishop, Caudell David L, Simpson R Mark, Kindt Thomas J
Molecular and Cellular Immunogenetics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg #50, Room 5515, 50 South Drive, Bethesda, MD 20892, USA.
Retrovirology. 2005 May 23;2:34. doi: 10.1186/1742-4690-2-34.
Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection.
A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1.
Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals.
人类嗜T淋巴细胞病毒1型（HTLV-1）感染患者的前病毒载量水平与临床结果相关，且具有合理的预后价值。本文研究了前病毒载量测量技术在HTLV-1感染实验兔模型中的应用。最初的研究试图在前病毒载量与该模型中的接种途径、剂量以及临床结果之间建立关联。这些方法有助于我们持续利用该模型来测试减轻病毒感染的治疗方法这一目标的实现。
使用实时聚合酶链反应（PCR）检测法测量了一系列兔子血液和组织样本中的前病毒载量，这些兔子通过接种以无细胞病毒颗粒、感染细胞或血液形式制备的HTLV-1接种物，或通过裸DNA注射进行感染。无症状感染兔子的前病毒载量水平与临床无症状HTLV-1感染人类患者的报告水平相当。在50%实验感染并出现自发良性或恶性肿瘤的兔子中，前病毒载量相应增加。在患有实验性诱导的急性白血病/淋巴瘤样疾病的兔子器官中也发现了类似升高的前病毒。尸检时获取的器官中的前病毒水平差异很大，这表明在传统上不被认为是HTLV-1靶标的非淋巴器官中存在感染库。
前病毒载量测量是对HTLV-1感染兔模型的一项有价值的补充，它提供了一种监测感染动物临床状态的指标，也是测试对抗感染治疗方法的手段。在某些情况下，血液中的前病毒载量并不能反映器官中的前病毒水平，这揭示了该方法在监测HTLV-1感染个体健康状况方面的局限性。
