HIV‐1 Nef triggers Vav‐mediated signaling pathway leading to functional and morphological differentiation of dendritic cells

• DOI: 10.1096/fj.03-0272com
• Publication Date: 2003-11-04T01:47:39Z
• Authors: Maria Giovanna Qu...; Benedetta Mattioli; Francesca Spadaro; Elisabetta Straface; Luciana Giordani; Carlo Ramoni; Walter Malorni; Marina Viora
• Keywords: Immunological synapse; Small GTPase

The accessory HIV-1 Nef protein plays a key role in AIDS pathogenesis. We recently demonstrated that exogenous triggers phenotypic and functional differentiation of immature dendritic cells (DCs). Here we investigated whether the Nef-induced DC occurs with morphological remodeling have focused on interference signaling pathways regulates maturation. found enters DCs, promoting their differentiation. Specifically, promotes interleukin (IL) -12 release, which closely fits nuclear factor (NF) -kappaB activation. induces rearrangement actin microfilaments, leading to uropod ruffle formation. Moreover, increases capacity DCs form clusters allogeneic CD4+ T cells, improving immunological synapse Searching for molecules involved Nef-triggered driving maturation, targets Vav its tyrosine phosphorylation, associated nucleus-to-cytoplasm redistribution. This has direct effect guanine nucleotide exchange activity small GTPase Rac1. hypothesize targeting Vav, modulates both early events (such as cytoskeletal rearrangement) delayed responses transcriptional regulation), Our results highlight how may enhance lymphocyte activation, thus fostering virus dissemination, manipulating arm immune response.