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

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.