Dual effect of interleukin 4 on HIV-1 expression: Implications for viral phenotypic switch and disease progression
Dual effect of interleukin 4 on HIV-1 expression: Implications for viral phenotypic switch and disease progression
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DOI：
10.1073/pnas.95.15.8886
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发表时间：
1998-07-21
影响因子：
11.1
通讯作者：
Pavlakis, GN
中科院分区：
文献类型：
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作者：
Valentin, A;Lu, WH;Pavlakis, GN
我们报告说，白细胞介素4（IL-4）抑制非合胞体诱导的传播和增加合胞体诱导的HIV-1分离株的传播通过两种机制。IL-4在人外周血单核细胞中差异调节两种主要的HIV-1辅助受体CCR 5和CXCR 4，增加CXCR 4和降低CCR 5在原代CD 4（+）T淋巴细胞中的表达。此外，IL-4通过转录激活机制刺激所有HIV-1分离株的表达。这些作用的组合导致使用CXCR 4的HIV-1菌株的增殖增加和使用CCR 5的HIV-1菌株的抑制。IL-4还激活原代单核细胞/巨噬细胞中的HIV-1表达，但不影响CCR 5表达。这些结果确定了IL-4作为HIV-1的重要调节因子，并表明这种细胞因子在控制病毒进化和从非合胞体诱导到合胞体诱导的表型转换中起关键作用，这导致加速疾病进展。
We report that interleukin 4 (IL-4) inhibits the propagation of non-syncytia-inducing and increases the propagation of syncytia-inducing HIV-1 isolates by two mechanisms. It differentially regulates the two major HIV-I coreceptors, CCR5 and CXCR4, in human peripheral blood mononuclear cells, increasing CXCR4 and decreasing CCR5 expression in primary CD4(+) T-lymphocytes, In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The combination of these effects results in increased propagation of CXCR4-using and inhibition of CCR5-using HIV-1 strains, IL-4 also activates HIV-1 expression in primary monocytes/macrophages but does not affect CCRS expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-inducing to syncytia-inducing, which leads to accelerated disease progression.