Submitted June 10, 2008
Accepted September 16, 2008
Cell adhesion through alphaV-containing integrins is required for efficient HIV-1 infection in macrophages
Ester Ballana, Eduardo Pauls, Jordi Senserrich, Bonaventura Clotet, Francoise Perron-Sierra, Gordon C. Tucker, and Jose A. Este*
Retrovirology Laboratory IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain
Institut de Recherches Servier, Departments of Medicinal Chemistry and Cancer Research and Drug Discovery, Croissy sur Seine, France
* Corresponding author; email: jaeste{at}irsicaixa.es.
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 alphaV integrin in monocyte-derived macrophages, by RNA interference or their inhibition by a selective small heterocyclic RGD-mimetic non-peptide compound, inhibited the replication of HIV in the absence of cytotoxicity. Interference or inhibition of alphaV integrins triggered a signal transduction pathway leading to downregulation of NF-kappaB dependent HIV-1 transcription. Such inhibition was mediated by a MAP-kinase signalling cascade, likely involving ERK1/2, p38-MAPK and HSP27. In conclusion, our results reveal a significant role of integrin alphaV-mediated adhesion in HIV-1 infection of macrophages.
