SDF-1-induced activation of ERK enhances HIV-1 expression

Chemokine receptors are not only able to bind chemokines but, together with CD4, they serve as an entry door for the human immunodeficiency virus type 1 (HIV-1). The signalling capacity of chemokine receptors, which is of fun damental importance for chemokine-induced chemotaxis, is not used by HIV-1 to enter a target cell, nor by chemokines or chemokine-derived ligands to i nhibit viral entry. In addition, an ill-defined signal triggered by chemoki nes can, under some circumstances, lead to an increase in HIV-1 expression. We show here that, in infected cells, exposure to SDF-1 leads to an increa sed expression of a X4 strain of HIV-1. A similar increase can be induced b y an N-terminal peptide of SDF-1 which had previously been shown to elicit an intracellular calcium response and to inhibit the entry of X4 strains of HIV-1. We demonstrate the involvement of extracellular signal-regulated ki nases (ERK) in this phenomenon. SDF-1 activates ERK-1 and ERK-2 in Jurkat c ells. In HeLa cells, ERK-2 only is activated by SDF-1 or by a SDF-derived p eptide. This ERK activation can be blocked by pertussis toxin and by the ME K inhibitor U0126. Most importantly, SDF-1-dependent HIV-1 expression is ab olished by pretreating the cells with pertussis toxin or with U0126. The co nsequences of this SDF-1-induced, ERK-dependent modulation of HIV-1 express ion in infected cells may have a clinical relevance for eradicating latent viruses.