Winters M A, Merigan T C
Center for AIDS Research, Stanford University Medical Center, California 94305.
AIDS Res Hum Retroviruses. 1993 Nov;9(11):1091-6. doi: 10.1089/aid.1993.9.1091.
CD4-PE40, a recombinant protein consisting of a portion of human CD4 linked to Pseudomonas aeruginosa exotoxin, was studied in vitro to assess its ability to inhibit the replication of primary isolates of HIV. CD4-PE40 was added to cultures of phytohemagglutin (PHA)-stimulated normal peripheral blood mononuclear cells (PBMCs) infected either with the laboratory strain HIVIIIb or single-passage virus stocks derived from patient PBMCs. Results showed that the replication of HIVIIIb was inhibited by a single pulse of CD4-PE40 and, more significantly, by continuous exposure to the drug. The replication of primary virus isolates, however, was inhibited only by continuous exposure to CD4-PE40. Cultures of freshly isolated PBMCs from HIV-seropositive individuals that were directly treated with CD4-PE40 before culture also required the continuous presence of drug to demonstrate inhibition of HIV replication. These results suggest that continuous administration of CD4-PE40 may be required to produce a significant anti-HIV effect in vivo.
CD4-PE40是一种重组蛋白，由与铜绿假单胞菌外毒素相连的一部分人CD4组成，在体外进行了研究，以评估其抑制HIV原代分离株复制的能力。将CD4-PE40添加到用植物血凝素（PHA）刺激的、感染了实验室菌株HIVIIIb或源自患者外周血单个核细胞（PBMC）的单传代病毒株的正常外周血单个核细胞（PBMC）培养物中。结果表明，HIVIIIb的复制受到单次脉冲CD4-PE40的抑制，更显著的是，受到持续接触该药物的抑制。然而，原代病毒分离株的复制仅受到持续接触CD4-PE40的抑制。在培养前直接用CD4-PE40处理的来自HIV血清阳性个体的新鲜分离PBMC培养物，也需要持续存在药物才能显示出对HIV复制的抑制作用。这些结果表明，可能需要持续给予CD4-PE40才能在体内产生显著的抗HIV效果。
