新型干扰素——IFN-λ抗HIV-1感染

An important role for type Ⅲ interferon（IFN-lambda） in anti-HIV activity

目的研究干扰素λ（IFN-λ）是否对HIV-1感染人巨噬细胞有抑制作用，并对可能介导IFN-λHIV-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理细胞24h，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体、CD4、CCR5、CXCR4的表达。结果IFN-λHIV-1感染人巨噬细胞具有明显抑制作用，且此作用与乓剂量及作用时间呈正相关。但IFN-λCD4、CCR5、CXCR4的表达影响无统计学意义。结论IFN-入能有效抑制HIV-1感染人臣噬细胞，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CD4、CCR5、CXCR4起作用而是存在有其他的抗病毒机制。

Objective 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-λ1/ IFN-λ2 for 24 h before infected by HIV-1 R5 strains （ Bal, Jago, and JRFL）. And then the culture supematants were detected HIV-1 reverse transcription （RT） activity and p24 protein expression by HIV-1 RT 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-1 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-1 infection of macrophages through connecting with IFN-λ receptor. Conclusion IFN-λ could inhibit HIV-1 replication in macrophages. These findings indicate that IFN-λ may have a therapeutic value in the treatment of HIV-1 infection.