IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
J Immunol. 2011 Jan 1;186(1):464-70. doi: 10.4049/jimmunol.1002693. Epub 2010 Nov 22.
Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. During the differentiation of monocytes to macrophages, adhesion molecules such as integrins are upregulated; therefore, they provide signals that control the process and subsequently may render macrophages more susceptible to HIV-1 infection. Previous work demonstrated that blocking α(v)-containing integrins triggered a signal transduction pathway leading to the inhibition of NF-κB-dependent HIV-1 transcription. In this paper, we show the influence of the different α(v)-coupled β integrins in HIV-1 replication in macrophages. Inhibition of β integrins, either by specific mAbs, small arginine-glycine-aspartic acid (RGD) mimetic compounds, or RNA interference, showed that integrin β(5) was the major contributor to the integrin-mediated blockade of HIV-1 replication. Importantly, such inhibition did not induce changes in cell adhesion to the substrate. In conclusion, our results reveal a significant role of the integrin dimer α(v)β(5) in HIV-1 infection of macrophages.
单核细胞和巨噬细胞是 HIV-1 感染的靶标，在病毒发病机制的多个方面发挥关键作用。在单核细胞分化为巨噬细胞的过程中，整合素等黏附分子上调；因此，它们提供了控制这一过程的信号，从而使巨噬细胞更容易感染 HIV-1。之前的工作表明，阻断含有 α(v)的整合素会触发一个信号转导途径，导致 NF-κB 依赖的 HIV-1 转录受到抑制。本文中，我们研究了不同的 α(v)偶联 β 整合素对巨噬细胞中 HIV-1 复制的影响。通过特异性 mAb、小精氨酸-甘氨酸-天冬氨酸 (RGD) 模拟化合物或 RNA 干扰抑制 β 整合素表明，整合素 β(5)是整合素介导的 HIV-1 复制阻断的主要贡献者。重要的是，这种抑制并没有诱导细胞对基质黏附的改变。总之，我们的结果揭示了整合素二聚体 α(v)β(5)在巨噬细胞感染 HIV-1 中的重要作用。
