Bazarbachi A, Saal F, Lasneret J, Poirot Y, Bittoun P, Hojman F, Périès J
UPR A0043 CNRS, Hôpital Saint-Louis, Paris, France.
C R Acad Sci III. 1994 Mar;317(3):264-9.
Ultrastructural studies on cell cultures derived from TSP/HAM and ATL patients, show the presence of large quantities of HTLV-I viral particles in extracellular spaces and budding at the cytoplasmic membrane. In addition, mature enveloped particles and images of endopinocytosis of virions are seen in the cytoplasm vacuoles suggesting the existence of a reinfection phenomenon. In this context, we decided to investigate some features of the replicative cycle, in particular the synthesis of unintegrated proviral forms. To increase the sensitivity of detection, we applied a procedure which combines the electrophoretic separation of closed circular forms and PCR amplification. By this procedure we produced evidence for the existence of supercoiled HTLV-I DNA in established cell lines from TSP/HAM and ATL and in patients peripheral blood mononuclear cells. These HTLV-I unintegrated proviral forms may play an important role in the physiopathology of HTLV-I associated diseases. Preliminary results of AZT/interferon treatment in ALT patients are largely superior to chemotherapy. The therapeutic effect of AZT, it known inhibitor of reverse transcriptase, may be through its inhibition of the synthesis of HTLV-I unintegrated proviral DNA.
对源自热带痉挛性截瘫/人类嗜T淋巴细胞病毒I型相关脊髓病（TSP/HAM）和成人T细胞白血病（ATL）患者的细胞培养物进行的超微结构研究表明，细胞外空间存在大量人类嗜T淋巴细胞病毒I型（HTLV-I）病毒颗粒，且在细胞质膜处出芽。此外，在细胞质空泡中可见成熟的包膜颗粒和病毒体的胞吞作用图像，这表明存在再感染现象。在此背景下，我们决定研究复制周期的一些特征，特别是未整合前病毒形式的合成。为了提高检测的灵敏度，我们采用了一种将闭环形式的电泳分离与聚合酶链反应（PCR）扩增相结合的方法。通过该方法，我们证明了在源自TSP/HAM和ATL的已建立细胞系以及患者外周血单个核细胞中存在超螺旋HTLV-I DNA。这些HTLV-I未整合前病毒形式可能在HTLV-I相关疾病的病理生理学中起重要作用。对ATL患者进行齐多夫定（AZT）/干扰素治疗的初步结果在很大程度上优于化疗。已知AZT是逆转录酶的抑制剂，其治疗效果可能是通过抑制HTLV-I未整合前病毒DNA的合成来实现的。
