Werner A, Winskowsky G, Kurth R
Paul-Ehrlich-Institute, Langen, Federal Republic of Germany.
J Virol. 1990 Dec;64(12):6252-6. doi: 10.1128/JVI.64.12.6252-6256.1990.
The CD4 molecule is expressed on T-helper cells and serves as the cellular receptor for the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for the simian immunodeficiency viruses SIVmac and SIVagm. HIV-1, HIV-2, and SIVmac infectivity can be blocked by monoclonal antibodies (MAbs) directed against the CD4 molecule and by soluble CD4 proteins (sCD4). In the present study, we demonstrated not only lack of inhibition, but 10- to 100-fold sCD4-dependent enhancement of SIVagm infectivity of human T-cell lymphoma lines, although SIVagm infection was blocked by MAbs OKT4a and Leu3a. SIVagm enhancement with sCD4 was suppressed by MAbs OKT4a and Leu3a to levels observed without addition of sCD4. The infectivity of all four tested SIVagm variants was enhanced by sCD4 on all tested lymphoma cell lines. These results suggest a second step (second or secondary receptor) required for enhancing virus entry into the cell and may have serious implications for approaches to the treatment of acquired immunodeficiency syndrome on the basis of modified sCD4 molecules.
CD4分子在辅助性T细胞上表达，是1型和2型人类免疫缺陷病毒（HIV-1和HIV-2）以及猴免疫缺陷病毒SIVmac和SIVagm的细胞受体。针对CD4分子的单克隆抗体（MAb）和可溶性CD4蛋白（sCD4）可阻断HIV-1、HIV-2和SIVmac的感染性。在本研究中，我们发现，尽管SIVagm感染可被MAb OKT4a和Leu3a阻断，但人T细胞淋巴瘤系的SIVagm感染性不仅没有受到抑制，反而在sCD4依赖的情况下增强了10至100倍。sCD4对SIVagm感染性的增强作用可被MAb OKT4a和Leu3a抑制至未添加sCD4时的水平。在所有测试的淋巴瘤细胞系上，sCD4均增强了所有四种测试的SIVagm变体的感染性。这些结果表明，病毒进入细胞的过程中存在增强作用所需的第二步（第二或辅助受体），这可能对基于修饰的sCD4分子治疗获得性免疫缺陷综合征的方法产生严重影响。
