Klatzmann D, Laporte J P, Achour A, Brisson E, Gruest J, Montagnier L, Gluckman J C
C R Acad Sci III. 1986;303(9):343-8.
The Human Immunodeficiency Virus (HIV) displays a selective tropism for cells expressing the CD4 molecule which, by itself, represents at least part of the specific receptor for this virus. However, modification of the activation state of each individual cell seems critical not only for virus replication but also for its binding and subsequent penetration into its target. We demonstrate here that Cyclosporin-A (CSA), a drug which inhibits IL-2 dependent T-lymphocyte proliferation and differentiation and which is known for its immunosuppressive activity, can prevent subsequent virus binding to cells otherwise susceptible to HIV. Normal T-lymphocytes were preincubated in vitro with CSA at concentrations that were in the same range than those reached in the serum of treated patients. This resulted in the complete disappearance of HIV receptors (HIV-R), as assessed by the direct measure of specific binding of fluoresceinated HIV (HIV-FITC), and in the subsequent inhibition of HIV replication in cultured cells. Moreover CSA pretreatment of IL-2 independent transformed cells derived from the CEM line, before their infection, strongly inhibited HIV adsorption as well as further virus replication. These results provide a new experimental basis for the potential application of CSA in the treatment of HIV-related diseases.
人类免疫缺陷病毒（HIV）对表达CD4分子的细胞表现出选择性嗜性，而CD4分子本身至少代表了该病毒特异性受体的一部分。然而，每个细胞激活状态的改变似乎不仅对病毒复制至关重要，而且对其与靶细胞的结合及随后的侵入也很关键。我们在此证明，环孢菌素A（CSA），一种抑制白细胞介素-2依赖性T淋巴细胞增殖和分化且以其免疫抑制活性而闻名的药物，能够阻止后续病毒与原本易感染HIV的细胞结合。正常T淋巴细胞在体外与CSA进行预孵育，其浓度与接受治疗患者血清中达到的浓度范围相同。通过直接测量荧光标记的HIV（HIV-FITC）的特异性结合来评估，这导致HIV受体（HIV-R）完全消失，并随后抑制了培养细胞中的HIV复制。此外，在源自CEM细胞系的白细胞介素-2非依赖性转化细胞感染前用CSA进行预处理，强烈抑制了HIV吸附以及进一步的病毒复制。这些结果为CSA在治疗HIV相关疾病中的潜在应用提供了新的实验依据。
