Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+T cells, mediated via cell signaling and Tat cofactor overexpression

Abstract : Objectives: The soluble HIV-1 gp120 envelope glycoprotein, after being shed from infected cells, can cross-link its receptors on both HIV-1 infected and non-infected target cells, leading to their activation. We have assessed the impact of soluble gp120 on viral replication in CD4+/CXCR4+ T cells, via its effects on Tat-mediated transactivation of the HIV-1/LTR. Materials and methods: Primary cord blood-derived CD4+/CXCR4+ T cells were stimulated with soluble recombinant gp120 (rgp120) from the HIV-1/HXB2 clone. The level of gene or protein expression was assessed by serial analysis gene expression (SAGE), reverse transcriptase-polymerase chain reaction, western blotting or flow-cytometry analysis. Cellular division of rgp120-stimulated T cells was assessed by CFDA-SE labeling. Long terminal repeat (LTR) activity and HIV infection level were respectively measured by a chemiluminescent P-gal Reporter Gene Assay and by p24 determination. Results: We have demonstrated that rgp120 activates both PKC epsilon and its upstream effector P13K/Akt, involved in the HIV-1 replication process. Moreover, rgp120 enhances the gene, as well as protein expression of the cellular Tat cofactors Tat-Sf1 and SPT5 in primary CD4+/CXCR4+ T cells. Finally, stimulation of HIV-1 infected T cells with rgp120 was found to result in both a higher LTR-activity and an increased production of viral particles. Conclusion: Taken together, these results show that soluble gp120 contributes to HIV-1 replication and dissemination, via the activation of multiple cell signaling pathways and the induction of Tat-cofactor expression, underscoring its potential as a therapeutic target in HIV-1-mediated pathogenesis. (c) 2005 Lippincott Williams & Wilkins.
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Submitted on : Friday, August 2, 2019 - 11:04:52 AM
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D. Misse, J. Gajardo, C. Oblet, A. Religa, N. Riquet, et al.. Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+T cells, mediated via cell signaling and Tat cofactor overexpression. AIDS, 2005, 19 (9), pp.897--905. ⟨hal-02262256⟩

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