AIDS Immunopathogenesis, San Raffaele Scientific Institute, Via Olgettina No. 58, Milan, Italy.
Blood. 2012 Mar 1;119(9):2013-23. doi: 10.1182/blood-2010-12-325308. Epub 2012 Jan 10.
Phytohemagglutin-stimulated child and adult leukocytes equally supported CCR5-dependent (R5) and CXCR4-dependent (X4) HIV-1 replication. In contrast, when phytohemagglutin-stimulated leukocytes from either healthy or congenitally immunodeficient children were cultured on feeder cells, they well supported R5, but not X4 HIV-1 replication, whereas both viruses equally spread in adult cells maintained in similar conditions. Both child and adult cells showed similar levels of proliferation and surface expression of CD4, CCR5, CXCR4, CD25, CD69, and HLA-DR. Lack of X4 HIV-1 replication in child versus adult cells was not caused by a differential expression of several known HIV-1 restriction factors. Similar levels of HIV DNA synthesis occurred in child cells infected with R5 and X4 viruses up to 48 hours after infection when R5 HIV-1 showed a significantly superior capacity to spread in culture than X4 virus. Cultured child cells well supported single round vescicular stomatitis virus-G pseudotyped virus replication, whereas superinfection of R5-infected cells with X4 HIV-1 (or vice versa) rescued the replication of this latter virus. Thus, child cells exposed to feeder cell culture represent a novel model system in which the superior capacity of R5 versus X4 viruses to spread can be investigated in primary, untransformed CD4(+) cells.
植物血凝素刺激的儿童和成人白细胞均支持 CCR5 依赖性（R5）和 CXCR4 依赖性（X4）HIV-1 复制。相比之下，当来自健康或先天性免疫缺陷儿童的植物血凝素刺激的白细胞在饲养细胞上培养时，它们很好地支持 R5，但不支持 X4 HIV-1 复制，而两种病毒在类似条件下培养的成人细胞中均能平等传播。儿童和成人细胞均表现出相似水平的增殖和 CD4、CCR5、CXCR4、CD25、CD69 和 HLA-DR 的表面表达。儿童细胞中缺乏 X4 HIV-1 复制并不是由于几种已知的 HIV-1 限制因子的差异表达所致。在感染后 48 小时内，感染 R5 和 X4 病毒的儿童细胞中均发生相似水平的 HIV DNA 合成，此时 R5 HIV-1 在培养中传播的能力明显优于 X4 病毒。培养的儿童细胞很好地支持单次轮状病毒-G 假型病毒复制，而 R5 感染细胞中超感染 X4 HIV-1（或反之亦然）可挽救后者病毒的复制。因此，暴露于饲养细胞培养的儿童细胞代表了一种新的模型系统，在此系统中可以在原发性、未转化的 CD4(+)细胞中研究 R5 与 X4 病毒传播能力的差异。
