G-protein signaling triggered by R5 human immunodeficiency virus type 1 increases virus replication efficiency in primary T lymphocytes.
The binding of R5 envelope to CCR5 during human immunodeficiency virus type 1 (HIV-1) entry provokes cell activation, which has so far been considered to have no effect on virus replication, since signaling-defective CCR5 molecules have been shown to function normally as HIV-1 coreceptors on transformed cells or mitogen-stimulated T lymphocytes. As the background state of activation of these cells might have biased the results, we performed experiments using the same approach but with nonactivated primary T lymphocytes. We now report that the single R126N mutation in the DRY motif, involved in G-protein coupling, results in a signaling-defective CCR5 coreceptor with a drastically impaired capacity to support HIV-1 infection.
Lin
Yea-Lih
YL
Laboratoire d'Immunologie, Hopital Saint Eloi, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France.
Mettling
Clément
C
Portalès
Pierre
P
Réant
Brigitte
B
Clot
Jacques
J
Corbeau
Pierre
P
D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000821:virology*; D014779:Virus Replication
D019713:Receptors, CCR5; D019204:GTP-Binding Proteins