@article{fdi:010042983, title = {{S}oluble {HIV}-1 gp120 enhances {HIV}-1 replication in non-dividing {CD}4+{T} cells, mediated via cell signaling and {T}at cofactor overexpression}, author = {{M}iss{\'e}, {D}oroth{\'e}e and {G}ajardo, {J}. and {O}blet, {C}. and {R}eliga, {A}. and {R}iquet, {N}. and {M}athieu, {D}. and {Y}ssel, {H}. and {V}eas, {F}rancisco}, editor = {}, language = {{ENG}}, abstract = {{O}bjectives: {T}he 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. {W}e have assessed the impact of soluble gp120 on viral replication in {CD}4+/{CXCR}4+ {T} cells, via its effects on {T}at-mediated transactivation of the {HIV}-1/{LTR}. {M}aterials and methods: {P}rimary cord blood-derived {CD}4+/{CXCR}4+ {T} cells were stimulated with soluble recombinant gp120 (rgp120) from the {HIV}-1/{HXB}2 clone. {T}he 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. {C}ellular division of rgp120-stimulated {T} cells was assessed by {CFDA}-{SE} labeling. {L}ong terminal repeat ({LTR}) activity and {HIV} infection level were respectively measured by a chemiluminescent {P}-gal {R}eporter {G}ene {A}ssay and by p24 determination. {R}esults: {W}e have demonstrated that rgp120 activates both {PKC} epsilon and its upstream effector {P}13{K}/{A}kt, involved in the {HIV}-1 replication process. {M}oreover, rgp120 enhances the gene, as well as protein expression of the cellular {T}at cofactors {T}at-{S}f1 and {SPT}5 in primary {CD}4+/{CXCR}4+ {T} cells. {F}inally, 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. {C}onclusion: {T}aken 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 {T}at-cofactor expression, underscoring its potential as a therapeutic target in {HIV}-1-mediated pathogenesis. (c) 2005 {L}ippincott {W}illiams and {W}ilkins.}, keywords = {{HIV} ; gp120 ; {T}at {S}f1 ; {SPT}5 ; {HIV} replication ; {CXCR}4}, booktitle = {}, journal = {{A}ids}, volume = {19}, numero = {9}, pages = {897--905}, ISSN = {0269-9370}, year = {2005}, URL = {https://www.documentation.ird.fr/hor/fdi:010042983}, }