Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages
Cell adhesion through αV-containing integrins is required for efficient HIV-1 infection in macrophages
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DOI：
10.1182/blood-2008-06-161869
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发表时间：
2009-02-05
期刊：
影响因子：
20.3
通讯作者：
Este, Jose A.
中科院分区：
文献类型：
--
作者：
Ballana, Ester;Pauls, Eduardo;Este, Jose A.
单核细胞和巨噬细胞是人类免疫缺陷病毒（HIV）的重要储存库，可能是组织中该病毒的最大储存库。单核细胞分化为巨噬细胞导致细胞附着和对HIV感染和复制的易感性。在其他细胞表面分子中，整合素在单核细胞-巨噬细胞分化期间过表达，并且可能在包膜病毒（包括HIV）的复制周期中发挥作用。在这里，我们表明，在单核细胞衍生的巨噬细胞中的α V整合素的抑制，通过RNA干扰或其抑制的选择性小杂环类RGD-模拟非肽化合物，抑制了HIV的复制在细胞毒性的情况下。干扰或抑制α V整合素触发了信号转导途径，导致核因子-κ B依赖性HIV-1转录下调。这种抑制是由MAP激酶信号级联介导的，可能涉及ERK 1/2，p38-丝裂原活化蛋白激酶和HSP 27。总之，我们的研究结果揭示了整合素α V介导的粘附在HIV-1感染巨噬细胞中的重要作用。（血。2009; 113：1278-1286）
Monocytes and macrophages are an important reservoir of human immunodeficiency virus (HIV) and may represent the largest reservoir of this virus in tissues. Differentiation of monocytes into macrophages leads to cell attachment and susceptibility to infection and replication of HIV. Among other cell-surface molecules, integrins are overexpressed during monocyte-macrophage differentiation and may play a role in the replication cycle of envelope viruses including HIV. Here, we show that inhibition of alpha V integrin in monocyte-derived macrophages, by RNA interference or their inhibition by a selective small heterocyclic RGD-mimetic nonpeptide compound, inhibited the replication of HIV in the absence of cytotoxicity. Interference or inhibition of alpha V integrins triggered a signal transduction pathway, leading to down-regulation of nuclear factor-kappa B-dependent HIV-1 transcription. Such inhibition was mediated by a MAP-kinase signaling cascade, probably involving ERK1/2, p38-mitogen-activated protein kinases, and HSP27. In conclusion, our results reveal a significant role of integrin alpha V-mediated adhesion in HIV-1 infection of macrophages. (Blood. 2009; 113: 1278-1286)