Cell adhesion through alphaV-containing integrins is required for efficient HIV-1 infection in macrophages.

Cell adhesion through alphaV-containing integrins is required for efficient HIV-1 infection in macrophages.

Data de publicació online: 05/02/2009 Revista: Blood

Abstract:

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 αV 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 αV integrins triggered a signal transduction pathway, leading to down-regulation of nuclear factor-κB–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 αV-mediated adhesion in HIV-1 infection of macrophages.

Autors: Ballana E, Pauls E, Senserrich J, Clotet B, Perron-Sierra F, Tucker GC, Esté JA.

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