β5 Integrin Is the Major Contributor to the αv Integrin-Mediated Blockade of HIV-1 Replication

被引:19
作者
Ballana, Ester
Pauls, Eduardo
Clotet, Bonaventura
Perron-Sierra, Francoise [2 ,3 ]
Tucker, Gordon C. [2 ]
Este, Jose A. [1 ]
机构
[1] Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, Lab Retrovirol, IrsiCaixa, Barcelona 08916, Spain
[2] Servier Res Inst, Dept Med Chem, Croissy Sur Seine, France
[3] Servier Res Inst, Dept Canc Res & Drug Discovery, Croissy Sur Seine, France
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; SMOOTH-MUSCLE-CELLS; MONOCYTE DIFFERENTIATION; MONONUCLEAR PHAGOCYTES; HUMAN MACROPHAGES; TYPE-1; INFECTION; ACTIVATION; EXPRESSION; ADHESION; MICE;
D O I
10.4049/jimmunol.1002693
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 alpha(v)-containing integrins triggered a signal transduction pathway leading to the inhibition of NF-kappa B-dependent HIV-1 transcription. In this paper, we show the influence of the different alpha(v)-coupled beta integrins in HIV-1 replication in macrophages. Inhibition of beta integrins, either by specific mAbs, small arginine-glycine-aspartic acid (RGD) mimetic compounds, or RNA interference, showed that integrin beta(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 dimmer alpha(v)beta(5) in HIV-1 infection of macrophages. The Journal of Immunology, 2011, 186: 464-470.
引用
收藏
页码:464 / 470
页数:7
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