Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes

摘要: Human homologue of the Drosophila Dlg tumor suppressor (hDlg) is a widely expressed scaffold protein implicated in organization multi-protein complexes at cell adhesion sites such as neuronal synapse. hDlg contains three PDZ domains that mediate its binding to consensus motifs present C-termini various surface proteins, thus inducing their clustering and/or stabilization plasma membrane. Using yeast two-hybrid screen, we identified cellular partner viral membrane integral protein, envelope glycoprotein (Env) human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 retrovirus infects CD4+ T lymphocytes and preferentially transmitted via direct contacts between infected target cells, through structure referred virological Here, demonstrate interacts with classical domain-binding motif C-terminus cytoplasmic domain Env conserved related HTLV-2 virus. We further document that, primary are concentrated restricted areas membrane, enriched molecules involved contacts. The presence Gag proteins responsible for assembly budding these indicated they constitute platforms transmission. Finally, mutant unable bind exhibited decreased ability trigger mediated fusion lymphocytes. propose stabilizes glycoproteins synapse formed hence assisting cell-to-cell transmission