Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: Implications for recruitment of leukocytes into brain and lymph nodes
Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: Implications for recruitment of leukocytes into brain and lymph nodes
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DOI：
10.1073/pnas.93.2.700
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发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
Sherry, B
中科院分区：
文献类型：
--
作者：
Schmidtmayerova, H;Nottet, HSLM;Sherry, B
人单核细胞感染人类免疫缺陷病毒1型(HIV-1)后，巨噬细胞炎性蛋白1α和1β(MIP-1α和MIP-1β)被诱导产生两种趋化因子(趋化细胞因子)β多肽。诱导依赖于有效的病毒感染：不仅MIP-1肽的诱导动力学与病毒复制的动力学密切相关，而且接种热灭活病毒或在AZT存在下感染的单核细胞培养物也不能产生这些趋化因子β肽。此外，HIV感染显著改变了由肿瘤坏死因子(TNF)诱导的β趋化因子的表达模式，肿瘤坏死因子本身是一种在艾滋病发展过程中上调的强有力的促炎细胞因子。对艾滋病痴呆患者脑组织进行逆转录聚合酶链式反应和原位聚合酶链式反应研究，结果显示MIP-1α和MIP-1β的mRNA表达高于HIV-1感染的非痴呆症患者的相应样本。在HIV-1感染的脑中，表达趋化因子的细胞在形态上被鉴定为小胶质细胞和星形胶质细胞。由于MIP-1a和MIP-1β对单核细胞和淋巴细胞亚群都有很强的趋化作用，这种β趋化因子表达的失调可能会影响HIV感染过程中白细胞的运输。这些数据综合起来，提出了一种机制，通过这种机制，感染HIV-1的单核细胞可能会将未感染的T细胞和单核细胞招募到病毒复制或炎症活跃的部位，特别是大脑和淋巴结。
Two chemokine (chemoattractant cytokines) beta peptides, macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta), were induced in human monocyte cultures following infection with the human immunodeficiency virus type 1 (HIV-1). Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these chemokine beta peptides. In addition, HIV infection markedly altered the pattern of beta chemokine expression elicited by tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR studies on brain tissue from patients with AIDS dementia demonstrated elevated MIP-1 alpha and MIP-1 beta mRNA expression relative to comparable samples from HIV-1-infected patients without dementia. Cells expressing chemokines in HIV-1-infected brains were identified morphologically as microglia and astrocytes. As MIP-la and MIP-1 beta are potent chemoattractants for both monocytes and specific subpopulations of lymphocytes, this dysregulation of beta chemokine expression may influence the trafficking of leukocytes during HIV infection. These data, taken together, suggest a mechanism by which HIV-1-infected monocytes might recruit uninfected T cells and monocytes to sites of active viral replication or inflammation, notably the brain and lymph nodes.