Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease
Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease
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DOI：
10.1128/jvi.75.5.2262-2275.2001
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发表时间：
2001-03-01
影响因子：
5.4
通讯作者：
Allan, JS
中科院分区：
文献类型：
--
作者：
Broussard, SR;Staprans, SI;Allan, JS
非洲绿猴可以长期持续感染猴免疫缺陷病毒(SIVagm)而不会发展成艾滋病，从而为理解自然宿主抵抗疾病的机制提供了一个重要的模型。这项研究评估了SIVagm在健康、自然感染的猴子中的水平和解剖分布。用定量竞争逆转录聚合酶链式反应方法检测两个非洲绿猴亚种的SIVagm，结果显示沙贝和斑尾猴的血浆中SIV RNA含量较高(>；6×10(6)RNA拷贝/毫升)。传染性病毒很容易从血浆和外周血单核细胞中恢复，并在人细胞系和巨噬细胞中表现出高度的细胞病变。SIVagm DNA水平在胃肠道中最高，表明肠道是体内SIVagm复制的主要部位。在脑实质和脑脊液中也发现了可察觉的病毒水平，在外周血细胞和淋巴结中检测到的病毒水平较低。来自脑脊液和脑实质的病毒分离株在培养中很容易感染巨噬细胞，而淋巴结分离株在人类T细胞系中更受限制。对env V2-C4序列的比较表明，从中枢神经系统和从淋巴组织中回收的SIVagm之间存在着广泛的氨基酸多样性。脑和脑脊液病毒之间的同源性、巨噬细胞的趋向性和活跃的复制表明，在自然感染的猴子中，中枢神经系统存在分区，而没有相关的神经病理。这些研究提供的证据表明，SIVagm在自然宿主中的非致病性既不能归因于宿主对病毒复制的更有效控制，也不能归因于组织和细胞嗜性与人类免疫缺陷病毒1型感染的人或SIV感染的猕猴的不同。
African green monkeys can maintain long-term persistent infection with simian immunodeficiency viruses (SIVagm) without developing AIDS and thus provide an important model for understanding mechanisms of natural host resistance to disease. This study assessed the levels and anatomic distribution of SIVagm in healthy, naturally infected monkeys. Quantitative competitive reverse transcriptase PCR assays developed to measure SIVagm from two African green monkey subspecies demonstrated high levels of SIV RNA in plasma (>6 x 10(6) RNA copies/ml) in sabaeus and vervet monkeys. Infectious virus was readily recovered from plasma and peripheral blood mononuclear cells and shown to be highly cytopathic in human cell lines and macrophages. SIVagm DNA levels were highest in the gastrointestinal tract, suggesting that the gut is a major site for SIVagm replication in vivo. Appreciable levels of virus were also found within the brain parenchyma and the cerebrospinal fluid (CSF), with lower levels detected in peripheral blood cells and lymph nodes. Virus isolates from the CSF and brain parenchyma readily infected macrophages in culture, whereas lymph node isolates were more restricted to growth in human T-cell lines. Comparison of env V2-C4 sequences showed extensive amino acid diversity between SIVagm recovered from the central nervous system and that recovered from lymphoid tissues. Homology between brain and CSF viruses, macrophage tropism, and active replication suggest compartmentalization in the central nervous system without associated neuropathology in naturally infected monkeys. These studies provide evidence that the nonpathogenic nature of SIVagm in the natural host can be attributed neither to more effective host control over viral replication nor to differences in the tissue and cell tropism from those for human immunodeficiency virus type 1-infected humans or SIV-infected macaques.