Salmon P, Olivier R, Riviere Y, Brisson E, Gluckman J C, Kieny M P, Montagnier L, Klatzmann D
Laboratoire de Biologie et Génétique des Déficits Immunitaires, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
J Exp Med. 1988 Dec 1;168(6):1953-69. doi: 10.1084/jem.168.6.1953.
Using mAbs and genomic probe to the CD4 molecule, the HIV receptor, we demonstrated that HIV replication induces the disappearance of its functional receptor from the cell surface by two distinct mechanisms. First, after being expressed onto the cell surface, HIV envelope gp110 will complex CD4, efficiently masking the CD4 epitope used by the virus to bind its receptor. This phenomenon occurs on the surface of each infected cell and is not due to the release of soluble gp110; infection with recombinant HIV/vaccinia viruses expressing a mutated HIV env gene designed to prevent gp110 release from the cell surface induces a similar gp/CD4 complexes formation. Second, virus replication induces a dramatic and rapid loss of CD4 mRNA transcripts, preventing new CD4 molecules from being synthesized. These two mechanisms of receptor modulation could have been developed to avoid reinfection of cells replicating the virus as well as to produce more infectious particles. These results suggest that the classical virus interference documented for other retroviruses might not only be due to receptor/envelope interaction, but might also depend on receptor gene expression.
利用针对HIV受体CD4分子的单克隆抗体（mAbs）和基因组探针，我们证明HIV复制通过两种不同机制导致其功能性受体从细胞表面消失。首先，HIV包膜糖蛋白gp110在表达到细胞表面后，会与CD4形成复合物，有效地掩盖病毒用于结合其受体的CD4表位。这种现象发生在每个受感染细胞的表面，并非由于可溶性gp110的释放；用表达经设计可防止gp110从细胞表面释放的突变HIV env基因的重组HIV/痘苗病毒感染，会诱导类似的gp/CD4复合物形成。其次，病毒复制导致CD4 mRNA转录本急剧快速减少，阻止新的CD4分子合成。受体调节的这两种机制可能是为了避免已复制病毒的细胞再次感染以及产生更多感染性颗粒而进化出来的。这些结果表明，其他逆转录病毒所记录的经典病毒干扰可能不仅归因于受体/包膜相互作用，还可能取决于受体基因表达。
