The Activity of Matrix Metalloproteinase-9 is Part of the Mechanism of Cell-to-Cell HIV-1 Endocytosis in Dendritic Cells

Eliana      Ruggiero; Elena      Toschi; Maurizio      Federico

Abstract

Human immunodeficiency virus (HIV) starts to replicate upon virus-cell fusion mediated by the CD4-Envcoreceptor interaction. HIV enters target cells also through endocytosis, a mechanism which rarely leads to HIV replication. Both modes of entry are greatly improved by cell-cell contact. We recently reported that the contact of human primary dendritic cells with HIV-1 infected cells leads to high levels of virus endocytosis and HIV-1 antigen presentation activity in dendritic cells. Here, we provide evidence that the activity of matrix metalloproteinase (MMP)-9 is involved in the mechanism of cell-to-cell HIV-1 endocytosis in DCs. Accordingly, the specific inhibition of MMP-9 led to reduced extents of HIV-1 antigen presentation activity. The identification of cell molecules involved in the cell-to-cell HIV-1 endocytosis would be of significance for better understanding the mechanisms underlying the induction of the anti-HIV adaptive immune response.

Keywords: Cell-to-cell HIV-1 endocytosis, dendritic cells, GM6001, matrix metalloproteinase-9, siRNAs, antigen presentation activity