Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression
Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression
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DOI：
10.1099/0022-1317-79-4-731
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发表时间：
1998-04-01
影响因子：
3.8
通讯作者：
Brack-Werner, R
中科院分区：
文献类型：
--
作者：
Wachinger, M;Kleinschmidt, A;Brack-Werner, R
抗菌肽是先天免疫的效应物，为宿主提供针对寄生虫入侵者的快速非特异性防御。在本报告中，评估了两种已充分表征的抗菌两亲肽（蜂毒肽和天蚕素）在亚毒性浓度下对急性感染细胞中人类免疫缺陷病毒 1 (HIV-1) 复制和基因表达的影响。传染性无细胞病毒的产生以剂量依赖性方式受到抑制，蜂毒肽的 ID50 值范围为 0.9-1.5 μM，天蚕素的 ID50 值范围为 2-3 μM。蜂毒肽对细胞相关病毒产生的影响分析表明，Gag 抗原和 HIV-1 mRNA 水平降低。使用 HIV 长末端重复 (LTR) 驱动的报告基因质粒进行的瞬时转染测定表明，蜂毒肽对活性具有直接抑制作用HIV LTR 的。在用蜂毒肽或天蚕素基因的逆转录病毒表达质粒稳定转染的人类细胞中，HIV LTR 活性也降低。结论是，蜂毒肽和天蚕素等抗菌肽能够通过抑制 HIV-1 基因表达来抑制细胞相关的 HIV-1 产生。
Antimicrobial peptides are effecters of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders. In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations. Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID50 values in the range 0.9-1.5 mu M for melittin and 2-3 mu M for cecropin, Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs, Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene, It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression.