Glushakova S, Baibakov B, Zimmerberg J, Margolis L B
Laboratory of Cellular and Molecular Biophysics, National Institutes of Health, Bethesda, Maryland 20892, USA.
AIDS Res Hum Retroviruses. 1997 Apr 10;13(6):461-71. doi: 10.1089/aid.1997.13.461.
It is now apparent that HIV infection leads to a gradual collapse of a complex system of lymphoid tissue. This collapse tends to be associated with a change in virus tropism from macrophages to T lymphocytes, and a change in phenotype from nonsyncytium inducing (NSI) to syncytium inducing (SI). An experimental system is required to study the role of this change in HIV pathogenesis in lymphoid tissue. Here we describe such a system. Histocultures of human lymphoid tissue preserve their general cytoarchitecture, including a network of follicular dendritic cells (FDCs). Histocultures of tonsils, adenoids, or lymph nodes support productive infection with various laboratory and primary isolates of HIV-1 of different tropism and phenotype and exhibit isolate-dependent CD4+ T lymphocyte depletion. A strong correlation between the extent of CD4+ T cell depletion and the SI/NSI phenotype of the isolates is demonstrated. AZT was used as a model drug to inhibit viral replication and CD4+ T cell depletion in lymphoid histocultures. HIV pathogenesis and the effect of antivirals can now be studied in human lymphoid tissue under controlled conditions in vitro.
现在很明显，HIV感染会导致淋巴组织复杂系统的逐渐崩溃。这种崩溃往往与病毒嗜性从巨噬细胞向T淋巴细胞的转变以及表型从非融合诱导（NSI）向融合诱导（SI）的转变有关。需要一个实验系统来研究这种变化在HIV淋巴组织发病机制中的作用。在此我们描述这样一个系统。人淋巴组织的组织培养物保留了其总体细胞结构，包括滤泡树突状细胞（FDC）网络。扁桃体、腺样体或淋巴结的组织培养物支持不同嗜性和表型的各种实验室及原始HIV-1分离株的有效感染，并表现出与分离株相关的CD4+ T淋巴细胞耗竭。结果表明，CD4+ T细胞耗竭程度与分离株的SI/NSI表型之间存在强烈相关性。使用齐多夫定（AZT）作为模型药物来抑制淋巴组织培养物中的病毒复制和CD4+ T细胞耗竭。现在可以在体外可控条件下，在人淋巴组织中研究HIV发病机制及抗病毒药物的作用。
