| Autor: |
Dufrasne FE; 1 Microbiology Unit (MBLG), AIDS Reference Laboratory (ARL), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium., Lucchetti M; 1 Microbiology Unit (MBLG), AIDS Reference Laboratory (ARL), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium., Dessilly G; 1 Microbiology Unit (MBLG), AIDS Reference Laboratory (ARL), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium., Ruelle J; 2 Clinical Laboratories Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium., Martin A; 1 Microbiology Unit (MBLG), AIDS Reference Laboratory (ARL), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium., Kabamba-Mukadi B; 1 Microbiology Unit (MBLG), AIDS Reference Laboratory (ARL), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium.; 2 Clinical Laboratories Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium. |
| Abstrakt: |
The cytoplasmic tail (CT) of the HIV-2 envelope glycoprotein (Env) includes amino acid (aa) sequences that are similar to lentiviral lytic peptides (LLP) described in other lentiviruses. Within the putative LLP-2 region, we previously observed insertions of 3 or 7 aa in sequences deduced from plasma viral RNA of symptomatic HIV-2-infected individuals. Based on these observations, we reproduced the insertions in a molecular clone to assess their impact on replicative fitness and cell death in vitro. Using a molecular clone of the HIV-2 ROD reference strain, site-directed mutagenesis experiments allowed the generation of plasmids with the insertion L 791 TAI or L 791 QRALTAI in the Env protein. The clone with 7 aa insertion enhanced viral release 8 to 11 times in infected T cells and cell viability was impaired by more than 20%, compared with the wild-type HIV-2 ROD virus. The effect of the 3 aa insertion was milder, with a nonsignificant trend to enhance viral replication and cell death compared with the wild-type virus. Interestingly, the insertions in the Env proteins did not induce a significant increase of viral infectivity, as revealed by the infectivity assay using TZM-bl cells. The insertions in the Env CT observed in vivo from disease progressors may, therefore, be involved in the higher viral load observed in these individuals. This study may open the way to the development of a prognostic marker related to the HIV-2 infection progression. |
