Ketas Thomas J, Klasse Per Johan, Spenlehauer Catherine, Nesin Mirjana, Frank Ines, Pope Melissa, Strizki Julie M, Reyes Gregory R, Baroudy Bahige M, Moore John P
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA.
AIDS Res Hum Retroviruses. 2003 Mar;19(3):177-86. doi: 10.1089/088922203763315678.
The small-molecule CCR5 antagonist SCH-C (SCH 351125) was tested for its ability to inhibit HIV-1 replication in peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells, immature dendritic cells (DCs), and macrophages. Inhibition of infection of PBMCs by virus associated with mature DC in trans was also studied. For comparison, the peptide-based fusion inhibitor T-20 and the CC-chemokine RANTES were also evaluated. Although some cell type-dependent differences in potency were observed, each of the three entry inhibitors was active against the replication of three different CCR5-using primary isolates in each cell type. CCR5-dependent HIV-1 infectivity, whether DC associated or not, is thus vulnerable to inhibitors that block the virus-cell fusion process by different mechanisms. Together, these results suggest that SCH-C and other entry inhibitors should be evaluated for their clinical potential as inhibitors of HIV-1 replication in several settings, including the prevention of maternal-infant transmission and the prevention of sexual transmission by topical application as a microbicide.
对小分子CCR5拮抗剂SCH-C（SCH 351125）抑制HIV-1在外周血单核细胞（PBMC）、脐血单核细胞、未成熟树突状细胞（DC）和巨噬细胞中复制的能力进行了测试。还研究了其对经转染与成熟DC相关的病毒感染PBMC的抑制作用。作为对照，还评估了基于肽的融合抑制剂T-20和CC趋化因子RANTES。尽管观察到了一些细胞类型依赖性的效力差异，但三种进入抑制剂中的每一种在每种细胞类型中均对三种不同利用CCR5的原代分离株的复制具有活性。因此，无论是否与DC相关，CCR5依赖性HIV-1感染性都易受通过不同机制阻断病毒-细胞融合过程的抑制剂的影响。这些结果共同表明，应评估SCH-C和其他进入抑制剂在多种情况下作为HIV-1复制抑制剂的临床潜力，包括预防母婴传播以及通过作为杀微生物剂局部应用预防性传播。
