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巨噬细胞嗜性毒株HIV1-PAR的特性:细胞嗜性、病毒/细胞进入及包膜糖蛋白的核苷酸序列

Characterization of HIV1-PAR, a macrophage-tropic strain: cell tropism, virus/cell entry and nucleotide sequence of the envelope glycoprotein.

作者信息

Schmidtmayerova H, Gayet O, Guettari N, Bolmont C, Hirsch I, Chermann J C

机构信息

Unité de Recherches INSERM U322 sur les Rétrovirus et Maladies Associées, Campus Universitaire de Luminy, Marseille, France.

出版信息

Res Virol. 1993 Jan-Feb;144(1):21-6. doi: 10.1016/s0923-2516(06)80007-5.

DOI:10.1016/s0923-2516(06)80007-5
PMID:8446773
Abstract

The HIV1-PAR strain, isolated from the cerebrospinal fluid of an HIV1-seropositive man suffering from encephalopathy, replicated well in cord blood lymphocytes, poorly in peripheral blood mononuclear cells, and to different levels in blood-derived macrophage (BDM) cultures prepared from different blood donors. In marked contrast to its replication in primocultures, it did not grow in CEM and U937 cell lines. HIV1-PAR production in BDM was inhibited by more than 90% after treatment with OKT4A or 13B8.2 monoclonal antibodies (mAb) binding to adjacent epitopes of the D1 domain of the CD4 molecules. A lower but significant inhibitory effect was observed after BDM treatment with BL4 and OKT4 mAb, directed to the D2 and D3 domain of the CD4 molecule, respectively. The entire HIV1-PAR envelope glycoprotein gene was amplified by polymerase chain reaction and sequenced. The deduced amino acid sequence of HIV1-PAR gp160 revealed the presence of 847 amino acids and 86% homology with the HIV1 LAV virus prototype. An alignment of the amino acid sequence of the envelope glycoprotein of HIV1-PAR and HIV1-LAV showed that the differences were mostly clustered within the five variable regions. Five CD4-binding domains, the gp120/gp41 cleavage site, the putative gp41 fusion domain and 21 out of the 22 cysteine residues were conserved in both isolates. The results further confirm the macrophage-tropic character of the HIV1-PAR virus.

摘要

从一名患有脑病的HIV1血清阳性男子的脑脊液中分离出的HIV1 - PAR毒株,在脐血淋巴细胞中复制良好,在外周血单核细胞中复制较差,在由不同献血者制备的血源巨噬细胞(BDM)培养物中的复制水平也各不相同。与其在原代培养物中的复制情况形成显著对比的是,它在CEM和U937细胞系中不生长。用与CD4分子D1结构域相邻表位结合的OKT4A或13B8.2单克隆抗体(mAb)处理后,BDM中HIV1 - PAR的产生受到90%以上的抑制。用分别针对CD4分子D2和D3结构域的BL4和OKT4 mAb处理BDM后,观察到较低但显著的抑制作用。通过聚合酶链反应扩增并测序了整个HIV1 - PAR包膜糖蛋白基因。HIV1 - PAR gp160推导的氨基酸序列显示有847个氨基酸,与HIV1 LAV病毒原型有86%的同源性。HIV1 - PAR和HIV1 - LAV包膜糖蛋白的氨基酸序列比对表明,差异大多集中在五个可变区内。两种分离株中五个CD4结合结构域、gp120/gp41裂解位点、假定的gp41融合结构域以及22个半胱氨酸残基中的21个都是保守的。这些结果进一步证实了HIV1 - PAR病毒的嗜巨噬细胞特性。

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