Missé Dorothée, Gajardo J., Oblet C., Religa A., Riquet N., Mathieu D., Yssel H., Veas Francisco. (2005). Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+T cells, mediated via cell signaling and Tat cofactor overexpression. Aids, 19 (9), p. 897-905. ISSN 0269-9370.
Titre du document
Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+T cells, mediated via cell signaling and Tat cofactor overexpression
Année de publication
2005
Auteurs
Missé Dorothée, Gajardo J., Oblet C., Religa A., Riquet N., Mathieu D., Yssel H., Veas Francisco
Source
Aids, 2005,
19 (9), p. 897-905 ISSN 0269-9370
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 and Wilkins.
Plan de classement
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010042983]
Identifiant IRD
fdi:010042983
