摘要目的 研究干扰素λ(IFN-λ)是否对HIV-1感染人臣噬细胞有抑制作用,并对可能介导IFN-λ抗HIV-1作用的受体和辅助受体表达水平进行研究,初步探讨其抗HIV-1感染的机制.方法 HIV-1毒株感染人巨噬细胞前用IFN-λ处理细胞24 h,感染后第4天、第8天以及第12天分别检测感染细胞上清中HIV-1逆转录酶(RT)活性和p24蛋白水平,并用实时定量PCR检测细胞上IFN-λ受体、CD4、CCR5、CXCR4的表达.结果 IFN-λ对HIV-1感染人巨噬细胞具有明显抑制作用,且此作用与其剂量及作用时间呈正相关.但IFN-λ对CD4、CCR5、CXCR4的表达影响无统计学意义.结论 IFN-λ能有效抑制HIV-1感染人口噬细胞,并证实这一作用是通过其受体发挥功能的.但IFN-λ介导的抗HIV-1作用不是通过CIM、CCR5、CXCR4起作用而是存在有其他的抗病毒机制.
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abstractsObjective To examine whether IFN-λ has the ability to inhibit HIV-1 infection of blood monocyte-derived macrophages and its mechanism(s). Methods Macrophages were pretreated with IFN-λ/ IFN-λ2 for 24 h before infected by HIV-1 R5 strains (Bal, Jago, and JRFL). And then the culture supernatants were detected HIV-1 reverse transcription (RT) activity and p24 protein expression by HIV-1 BT assay and ELISA. The expressions of IFN-λ receptor, CD4, CCRS, CXCR4 were evaluated by real-time PCR. Results Both IFN-λ1 and IFN-λ2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-λ-mediated anti-HIV-I activity is broad, as IFN-λ could inhibit infection by both laboratory-adapted and clinical strains of HIV-1. Investigations of mechanism(s) responsible for the IFN-λ action showed that although IFN-λ had little effect on HIV-1 entry receptor CD4 and co-receptor CCR5 and CXCR4 expression, IFN-λ inhibited HIV-I infection of macrophages through connecting with IFN-λ recep-tor. Conclusion IFN-λ could inhibit HIV-I replication in macrophages. These findings indicate that IFN-λ may have a therapeutic value in the treatment of HIV-1 infection.
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