HIV-1B gp120 genes from one patient with AIDS dementia complex can affect the secretion of tumor necrosis factor and interleukin lp in glial cells

Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion...

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Published in:中华医学杂志：英文版 2011 (24), p.4217-4222
Main Author: YAN Yu-fen WANG Zhi-yu PU Shuang-shuang WEN Hong-ling HUANG Tao SONG Yan-yan XU Hong-zhi ZHAO Li
Format: Article
Language:English
Subjects:
基因多样性
痴呆
白细胞介素
神经胶质细胞
细胞分泌
肿瘤坏死因子
艾滋病毒感染
重组逆转录病毒
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Summary:Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-a by peripheral blood mononuclear cell （PBMC）; however, whether the difference of gp120 gene could affect the secretion of TNF-a and IL-113 by glial cells is unknown. The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines. Methods In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex （ADC）. Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120, pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells. Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately. Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree. Compared to the pMIG retrovirus （gp120-negative） or U87 cells, all the gp120-positive recombinant retroviruses induced more TNF-a （P 〈0.01） and IL-113 （P 〈0.01）. In addition, compared with the L/MIG retrovirus, all the three brain gp120-positive recombinant retroviruses induced less TNF-α （P 〈0.01） and IL-1β （P 〈0.01）. Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again. The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1 β, which might supply a novel idea helping understand the pathogenesis of ADC.
ISSN:0366-6999
2542-5641