Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans
Human immunodeficiency virus type 1 attachment to HeLa CD4 cells is CD4 independent and gp120 dependent and requires cell surface heparans
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DOI：
10.1128/jvi.72.5.3623-3634.1998
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发表时间：
1998-05-01
影响因子：
5.4
通讯作者：
Sattentau, QJ
中科院分区：
文献类型：
--
作者：
Mondor, I;Ugolini, S;Sattentau, QJ
采用一种基于抗HLA-DR特异性抗体检测HLA-DR+病毒与HLA-DR-细胞结合的新方法，分析了人类免疫缺陷病毒1型（HIV-1）（Hx 10）病毒粒子与两种不同细胞系的结合。病毒粒子对CD 4（+）-T细胞系A3.01的附着是高度CD 4依赖性的，因为它被CD 4单克隆抗体（MAbs）强效抑制，并且观察到很少的病毒与CD 4（-）姐妹细胞系A2.01结合。相比之下，病毒粒子与表达中等或高水平CD 4的HeLa细胞的结合相当于或低于与野生型CD 4（-）HeLa细胞的结合。此外，几种CD 4单克隆抗体没有减少，但增强，HIV-1附着到HeLa-CD 4细胞。CD 4是必需的HeLa细胞的感染，但是，表现出后附着的作用，这种受体。特异于V2和V3环以及gp 120的CD 4 i表位的MAbs强烈抑制病毒粒子与HeLa-CD 4细胞的结合，而特异于CD 4 bs和2G 12表位的MAbs增强了病毒粒子与HeLa-CD 4细胞的附着。尽管如此，测试的所有gp 120和gp 41特异性MAb中和了对HeLa-CD 4细胞的感染性，HIV-1对HeLa细胞的附着仅被对病毒或靶细胞上存在的粘附分子特异性的MAb部分抑制，但被聚阴离子如肝素、硫酸葡聚糖和硫酸戊聚糖完全阻断。用肝素酶处理HeLa-CD 4细胞完全消除了HIV附着和感染，强烈暗示细胞表面肝素在附着过程中。因此，HIV-1附着于靶细胞的CD 4依赖性是高度细胞系特异性的，并且可以被其他配体-受体相互作用所取代。
The binding of human immunodeficiency virus type 1 (HIV-1) (Hx10) virions to two different cell lines was analyzed by using a novel assay based on the detection, by anti-HLA-DR-specific antibodies, of HLA-DR+ virus binding to HLA-DR- cells. Virion attachment to the CD4(+)-T-cell line A3.01 was highly CD4 dependent in that it was potently inhibited by CD4 monoclonal antibodies (MAbs), and little virus binding to the CD4(-) sister A2.01 line was observed. By contrast, virion binding to HeLa cells expressing moderate or high levels of CD4 was equivalent to, or lower than, binding to wild-type CD4(-) HeLa cells. Moreover, several CD4 MAbs did not reduce, but enhanced, HIV-1 attachment to HeLa-CD4 cells. CD4 was required for infection of HeLa cells, however, demonstrating a postattachment role for this receptor. MAbs specific for the V2 and V3 loops and the CD4i epitope of gp120 strongly inhibited virion binding to HeLa-CD4 cells, whereas MAbs specific for the CD4bs and the 2G12 epitopes enhanced attachment. Despite this, all gp120- and gp41-specific MAbs tested neutralized infectivity on HeLa-CD4 cells, HIV-1 attachment to HeLa cells was only partially inhibited by MAbs specific for adhesion molecules present on the virus or target cells but was completely blocked by polyanions such as heparin, dextran sulfate, and pentosan sulfate. Treatment of HeLa-CD4 cells with heparinases completely eliminated HIV attachment and infection, strongly implicating cell surface heparans in the attachment process. CD4 dependence for HIV-1 attachment to target cells is thus highly cell line specific and may be replaced by other ligand-receptor interactions.