Brodie S J
University of Washington School of Medicine, Virology Division, Seattle 98195, USA.
J Leukoc Biol. 2000 Sep;68(3):351-9.
Autopsy tissues from 2 cohorts of age-matched HIV-infected children with similar plasma viral load (>10(5) HIV RNA copies/ml), but with distinct AIDS-associated disease manifestations, were examined for sites of persistent HIV replication. One group consisted of 3 children with severe lymphoid atrophy and peripheral blood CD4+ T cell counts of < 10/mm . Another group was composed of 6 children with extensive hyperplasia of mucosal-associated lymphoid tissues and blood CD4+ T cell counts >500/mm3. Hyperplastic bronchiole- and gut-associated lymphoid tissues were characterized by extensive networks of germinal center follicular dendritic cells (FDC) containing large amounts of immune-complexed virion RNA. Conversely, pulmonary and gastrointestinal tissues from children with severe CD4+ T cell depletion were devoid of any secondary lymphoid structures, yet these tissues also harbored high concentrations of HIV RNA. Dual in situ procedures showed that only macrophage (Mphi) within these sites contained tat fusion transcripts, a product of post-transcriptional splicing and a correlate of productive infection. When examining explant cultures of Mphi and FDC, only Mphi harbored HIV tat mRNA and only Mphi demonstrated budding retroviral particles. Hence, germinal center FDC in secondary lymphoid tissues are key reservoirs of immune-complexed HIV RNA and are likely to contribute to AIDS-associated lymphoproliferations; however, these cells do not support HIV replication, and failure to do so results from a post-transcriptional block in the virus life cycle. Moreover, gut and pulmonary Mphi represent a lineage of cells that are permissive to HIV replication and contribute significantly to the high viral load in children with severe CD4+ T cell depletion. It will be important to identify the molecular mechanisms that allow for these highly productive infections of Mphi.
对来自2组年龄匹配、血浆病毒载量相似（>10⁵ HIV RNA拷贝/ml）但艾滋病相关疾病表现不同的HIV感染儿童的尸检组织进行检查，以确定HIV持续复制的部位。一组由3名严重淋巴萎缩且外周血CD4⁺ T细胞计数<10/mm³的儿童组成。另一组由6名黏膜相关淋巴组织广泛增生且血液CD4⁺ T细胞计数>500/mm³的儿童组成。增生的细支气管和肠道相关淋巴组织的特征是生发中心滤泡树突状细胞（FDC）广泛网络，其中含有大量免疫复合物形式的病毒体RNA。相反，严重CD4⁺ T细胞耗竭儿童的肺和胃肠道组织没有任何二级淋巴结构，但这些组织也含有高浓度的HIV RNA。双重原位程序显示，这些部位只有巨噬细胞（Mphi）含有tat融合转录本，这是转录后剪接的产物，也是 productive感染的一个相关指标。在检查Mphi和FDC的外植体培养物时，只有Mphi含有HIV tat mRNA，只有Mphi显示出出芽的逆转录病毒颗粒。因此，二级淋巴组织中的生发中心FDC是免疫复合物形式的HIV RNA的关键储存库，可能导致艾滋病相关的淋巴增殖；然而，这些细胞不支持HIV复制，而无法支持复制是由于病毒生命周期中的转录后阻滞。此外，肠道和肺巨噬细胞代表了一类允许HIV复制的细胞谱系，并对严重CD4⁺ T细胞耗竭儿童的高病毒载量有显著贡献。确定允许巨噬细胞进行这些高效感染的分子机制将很重要。
