Fraternale A, Casabianca A, Orlandi C, Cerasi A, Chiarantini L, Brandi G, Magnani M
Institute of Biological Chemistry 'Giorgio Fornaini', University of Urbino, Via Saffi, 2 61029 (PU), Italy.
Antiviral Res. 2002 Dec;56(3):263-72. doi: 10.1016/s0166-3542(02)00128-6.
Monocyte-macrophages play a central role in HIV-1 infection because they are among the first cells to be infected and because later they are important reservoirs for the virus. Thus, newly designed therapies should take into account the protection of this cell compartment. Herein, we report the results obtained in a murine AIDS model, by the addition to AZT+DDI of a system (GSH-loaded erythrocytes) able to protect macrophages against HIV-1 infection. Five groups of LP-BM5-infected mice were treated as follows: one group was treated by AZT, one group was treated by DDI, one group was treated by the combination of both, another by GSH-loaded erythrocytes, and finally, one by the combination of all three. After 10 weeks of infection the parameters of the disease were studied and the proviral DNA content in different organs and in macrophages of bone marrow and of the peritoneal cavity was quantified. The results obtained show that mice treated with AZT+DDI+GSH-loaded erythrocytes showed proviral DNA content in the brain and in macrophages of bone marrow that was significantly lower than in mice treated with AZT+DDI. This study may help developing strategies aimed at blocking HIV-1 replication in its reservoirs in the body.
单核细胞 - 巨噬细胞在HIV - 1感染中起核心作用，因为它们是最早被感染的细胞之一，并且后来它们是该病毒的重要储存库。因此，新设计的疗法应考虑对这一细胞区室的保护。在此，我们报告在小鼠艾滋病模型中获得的结果，通过在齐多夫定（AZT）+双脱氧肌苷（DDI）基础上加用一种能够保护巨噬细胞免受HIV - 1感染的系统（负载谷胱甘肽的红细胞）。将五组感染LP - BM5的小鼠进行如下治疗：一组用AZT治疗，一组用DDI治疗，一组用两者联合治疗，另一组用负载谷胱甘肽的红细胞治疗，最后一组用三者联合治疗。感染10周后，研究疾病参数，并对不同器官以及骨髓和腹腔巨噬细胞中的前病毒DNA含量进行定量。所获得的结果表明，用AZT + DDI +负载谷胱甘肽的红细胞治疗的小鼠，其大脑和骨髓巨噬细胞中的前病毒DNA含量显著低于用AZT + DDI治疗的小鼠。这项研究可能有助于制定旨在阻断HIV - 1在其体内储存库中复制的策略。
