CD4 antigen-based antireceptor peptides inhibit infectivity of human immunodeficiency virus in vitro at multiple stages of the viral life cycle.
CD4 antigen-based antireceptor peptides inhibit infectivity of human immunodeficiency virus in vitro at multiple stages of the viral life cycle.
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基于 CD4 抗原的抗受体肽在病毒生命周期的多个阶段在体外抑制人类免疫缺陷病毒的感染性。
DOI：
10.1073/pnas.86.18.7139
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发表时间：
1989
影响因子：
11.1
通讯作者：
Lee E. Eiden
中科院分区：
文献类型：
--
作者：
Peter L. Nara;K. M. Hwang;Dianne M. Rausch;J. Lifson;Lee E. Eiden
CD4分子残基81 ~ 92对应肽的苯基化衍生物[CD4-(81-92)]在体外抑制人类免疫缺陷病毒1 （HIV-1）诱导的细胞融合和感染。如果这些多肽被认为是治疗HIV感染的候选药物，那么了解基于cd4的多肽的抗HIV功效是否仅限于阻断感染和病毒诱导的细胞融合，或者这些化合物是否会影响病毒生命周期的其他阶段是至关重要的。因此，根据病毒生命周期的两个一般阶段，将急性HIV感染的体外定量微量测定分为两个动力学阶段：(i)病毒感染和（ii）通过细胞接触或释放游离病毒粒子传播病毒和病毒蛋白产物。CEM-SS细胞培养在感染或传播阶段用肽处理。当在感染阶段存在多肽时，当暴露于病毒的细胞被清洗并复制到新鲜的未感染的指示细胞上时，合胞体形成的抑制与病毒核心蛋白p24的表达减少和缺乏感染性细胞中心相关。这些数据与仅在初次接触病毒时肽存在时病毒感染完全抑制一致。出乎意料的是，即使在接种后48小时，在实验的传播期间添加肽，也可以观察到合胞体形成的平行抑制，p24水平的降低和传染性细胞中心形成的抑制。由于在该检测系统中，病毒结合和渗透在48小时前就完成了，CD4-(81-92)肽衍生物似乎对已经感染HIV-1的培养物发挥了病毒抑制作用，降低了p24的产生、细胞致病性和细胞介导的感染性。
Benzylated derivatives of peptides corresponding to residues 81 through 92 of the CD4 molecule [CD4-(81-92)] inhibit human immunodeficiency virus 1 (HIV-1)-induced cell fusion and infection in vitro. If such peptides are to be considered as candidates in the therapy of HIV infection, it is crucial to know if the anti-HIV efficacy of CD4-based peptides is limited to blockade of infection and virus-induced cell fusion or if other stages of the viral life cycle are affected by these compounds. Accordingly, an in vitro quantitative microassay for acute HIV infection was divided into two kinetic phases corresponding to the two general stages of the viral life cycle: (i) viral infection and (ii) transmission of virus and viral protein products through cell contact or release of free virions. CEM-SS cell cultures were treated with peptide during either the infection or the transmission phase of the assay. When peptides were present during the infection phase, inhibition of syncytium formation correlated with decreased expression of viral core protein p24 and lack of infectious cell centers when cells exposed to virus were washed and replated onto fresh uninfected indicator cells. These data are consistent with complete inhibition of viral infection when peptide is present only during initial exposure to virus. Unexpectedly, parallel inhibition of syncytium formation, decreased p24 levels, and inhibition of infectious cell center formation were also seen even when peptides were added as late as 48 hr after inoculation, during the transmission period of the assay. Since viral binding and penetration are completed well before 48 hr in this assay system, CD4-(81-92) peptide derivatives appear to exert a virostatic effect on cultures already infected with HIV-1, decreasing p24 production, cytopathicity, and cell-mediated infectivity.