Identification of shared populations of human immunodeficiency virus type 1 infecting microglia and tissue macrophages outside the central nervous system
Identification of shared populations of human immunodeficiency virus type 1 infecting microglia and tissue macrophages outside the central nervous system
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DOI：
10.1128/jvi.75.23.11686-11699.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Simmonds, P
中科院分区：
文献类型：
--
作者：
Wang, TH;Donaldson, YK;Simmonds, P
人类免疫缺陷病毒I型(HIV-1)感染中枢神经系统(CNS)中的小胶质细胞和其他巨噬细胞/单核细胞系细胞是巨细胞性脑炎(GCE)发生的基础。目前尚不清楚GCE是否依赖于单核/巨噬细胞系细胞中是否出现专门适合复制的病毒群体，以及这是否也导致其他非淋巴组织中的巨噬细胞被特异性靶向。来自淋巴结、脑(额区)、肺和全层结肠切片的尸检样本来自9名GCE受试者和9名非GCE受试者。两组在CD4计数、疾病进展或死亡前的治疗史方面没有显著差异。通过对V3和p17(Gag)区域的序列比较，利用一种新开发的方法对相邻连接树中连续节点的样本成分进行评分，评估了从淋巴结和非淋巴组织中恢复的变异体之间的遗传相关性。关联指数使得能够对组织分区的程度进行客观的、数值的比较。高前病毒负荷和脑内p24抗原的表达仅限于9例GCE患者。GCE还与结肠样本中显著较高的前病毒负荷相关(GCE(+)组的中位数：1,010拷贝/10(6)个细胞；GCE(-)组的中位数，10/10(6)个细胞；P=0.006)。相比之下，在淋巴或肺样本中，GCE(+)组和GCE-组之间的前病毒载量没有显著差异，在这些样本中，HIV感染主要表现为淋巴细胞的渗透。来自GCE患者大脑样本的V3序列显示出与淋巴组织的V3序列最大的区隔，尽管来自其他组织的样本，特别是结肠组织的样本，经常含有与大脑中发现的V3序列在系统发育上相关的变体。两名GCE患者肺和结肠标本中CD68(+)、表达p24抗原的多核巨细胞的免疫细胞化学检测进一步表明，在GCE患者的单核/巨噬细胞谱系的细胞中存在共同的、不同的HIV群体。这项研究为未来可能的表型相似性的研究提供了基础，这些表型相似性强调了感染中枢神经系统外的小胶质细胞和组织巨噬细胞的HIV变异的共同分布。
Infection of microglia and other cells of the macrophage/monocyte lineage in the central nervous system (CNS) by human immunodeficiency virus type I (HIV-1) underlies the development of giant cell encephalitis (GCE). It is currently unknown whether GCE depends on the emergence of virus populations specifically adapted to replicate in cells of the monocyte/macrophage lineage and whether this also leads to the specific targeting of macrophages in other nonlymphoid tissues. Autopsy samples from lymph node, brain (frontal region), lung, and full-thickness colon sections were obtained from nine study subjects with GCE and from nine without. The two groups showed no significant differences in CD4 counts, disease progression, or treatment history before death. Genetic relatedness between variants recovered from lymph node and nonlymphoid tissues was assessed by sequence comparison of V3 and p17(gag) regions using a newly developed method that scores the sample composition at successive nodes in a neighbor-joining tree. The association index enabled objective, numerical comparisons on the degree of tissue compartmentalization to be made. High proviral loads and p24 antigen expression in the brain were confined to the nine individuals with GCE. GCE was also associated with significantly higher proviral loads in colon samples (median of the GCE(+) group: 1,010 copies/10(6) cells; median of GCE(-) group, 10/10(6) cells; P = 0.006). In contrast, there were no significant differences in proviral load between the GCE(+) and GCE- groups in lymph node or lung samples, where HIV infection was manifested predominantly by infiltrates of lymphoid cells. V3 sequences from brain samples of individuals with GCE showed the greatest compartmentalization from those of lymph node, although samples from other tissues, particularly the colon, frequently contained variants phylogenetically, related to those found in brain. The existence of shared, distinct populations of HIV specifically distributed in cells of the monocyte/macrophage lineage was further indicated by immunocytochemical detection of CD68(+), multinucleated giant cells expressing p24 antigen in samples of lung and colon in two individuals with GCE. This study provides the basis for future investigation of possible phenotypic similarities that underline the shared distributions of HIV variants infecting microglia and tissue macrophages outside the CNS.