Crise B, Buonocore L, Rose J K
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510-8023.
J Virol. 1990 Nov;64(11):5585-93. doi: 10.1128/JVI.64.11.5585-5593.1990.
We analyzed coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells to determine whether the two molecules can interact prior to transport to the cell surface. Results of studies employing coprecipitation, analysis of oligosaccharide processing, and immunocytochemistry showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER). CD4 expressed by itself was transported efficiently from the ER to the cell surface, but the complex of CD4 and gp160 was retained in the ER. This retention of CD4 within the ER is probably a consequence of the very inefficient transport of gp160 itself (R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Proc. Natl. Acad. Sci. USA 85:9580-9584, 1988). Retention of CD4 in the ER by gp160 may partially explain the down regulation of CD4 in human immunodeficiency virus type 1-infected T cells. Inhibition of CD4 transport appears to be a consequence of the interaction of two membrane-bound molecules, because a complex of CD4 and gp120 (the soluble extracellular domain of gp160) was transported rapidly and efficiently from the ER.
我们分析了人类免疫缺陷病毒1型糖蛋白前体gp160及其细胞受体CD4在HeLa细胞中的共表达情况，以确定这两种分子在转运至细胞表面之前是否能够相互作用。采用共沉淀、寡糖加工分析和免疫细胞化学的研究结果表明，新合成的CD4和gp160在内质网（ER）转运之前就形成了复合物。单独表达的CD4能有效地从内质网转运至细胞表面，但CD4与gp160的复合物则保留在内质网中。CD4在内质网中的滞留可能是gp160自身转运效率极低的结果（R.L.威利、J.S.博尼法西诺、B.J.波茨、M.A.马丁和R.D.克劳斯纳，《美国国家科学院院刊》85:9580 - 9584，1988）。gp160导致CD4在内质网中的滞留可能部分解释了人类免疫缺陷病毒1型感染的T细胞中CD4的下调。CD4转运的抑制似乎是两个膜结合分子相互作用的结果，因为CD4与gp120（gp160的可溶性细胞外结构域）的复合物能快速有效地从内质网转运。
