Barbouche R, Fenouillet E, Papandréou M J, Kiény M P, Sabatier J M
CNRS, Faculté de Médecine Nord, Marseille, France.
J Pept Res. 1998 Oct;52(4):283-8. doi: 10.1111/j.1399-3011.1998.tb01242.x.
A multibranched peptide construct (SPC3) derived from the conserved sequence of the third variable domain (V3) of the human immunodeficiency virus (HIV) envelope (Env) inhibits HIV infectivity. It is being tested in phase II clinical trials (FDA protocol 257A). Because some Env-derived peptides inhibit HIV infectivity through alteration of Env biosynthetic pathway, we studied whether SPC3 displays its activity through interference with Env biosynthesis or with its functions at the membrane. Syncytium formation was impaired when human CD4+ cells expressed recombinant HIV Env in the presence of SPC3. This inhibition was not due to an effect of SPC3 on the amount of Env expressed at the cell membrane. As assessed using antibodies, the conformation of the receptor binding site and of V3 presented on membrane Env was not affected by the presence of SPC3 during biosynthesis. Finally, despite the ability of SPC3 to bind to CD4+ cell membrane, SPC3 did not interfere with Env binding to CD4. These data suggest that SPC3 interferes with the infection process at a post-CD4 binding step, and not with the folding of Env.
一种源自人类免疫缺陷病毒（HIV）包膜（Env）第三个可变区（V3）保守序列的多分支肽构建体（SPC3）可抑制HIV感染性。它正在进行II期临床试验（FDA方案257A）。由于一些源自Env的肽通过改变Env生物合成途径来抑制HIV感染性，我们研究了SPC3是通过干扰Env生物合成还是其在膜上的功能来发挥其活性的。当人类CD4+细胞在SPC3存在的情况下表达重组HIV Env时，合胞体形成受到损害。这种抑制不是由于SPC3对细胞膜上表达的Env量的影响。使用抗体评估时，在生物合成过程中，SPC3的存在并不影响膜Env上呈现的受体结合位点和V3的构象。最后，尽管SPC3能够结合到CD4+细胞膜上，但SPC3并不干扰Env与CD4的结合。这些数据表明，SPC3在CD4结合后的步骤干扰感染过程，而不是干扰Env的折叠。
