title: Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis?
abstract: The release of virions from HIV-1-infected CD4 cells, although occurring readily as a result of immune activation, does not appear to be the only mechanism mediating T-cell loss in AIDS. Three other interacting HIV-1-induced immune disorders in association with viral release (the source of gp120 molecules) may also account for the constitutive T-cell depletion and functional immune suppression: 1. gp120-induced CD4(+) cell anergy, which can be reproduced in cultures of immune activated normal T-cells in the presence of gp120 or gp120 peptide containing the SLWDQ sequence identity to the CD4 molecule; 2. overproduction of IFNalpha and gamma, 3. activation-driven apoptosis of non infected T-cells. Apoptosis of T-cells could also be: 1. induced by effector components - particularly CTL and lymphotoxins produced by helper T-cells of the anti-Fas autoimmune reaction triggered by gp120 epitopes shared with the Fas/APO-1 molecule; 2. enhanced by IFN overproduction. These molecular mechanisms stress the importance in the progression to AIDS of both the viral load and HIV-induced cytokine dysregulation, including overproduction of IFNalpha, which should be considered as targets in the development of strategies for AIDS prophylaxis and immunotherapy.
authors.affiliation: Université Pierre et Marie Curie, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Zagury
authors.forename: V
authors.initials: V
authors.lastname: Chams
authors.forename: A
authors.initials: A
authors.lastname: Lachgar
authors.forename: A
authors.initials: A
authors.lastname: Achour
authors.forename: B
authors.initials: B
authors.lastname: Bizzini
authors.forename: A
authors.initials: A
authors.lastname: Burny
authors.forename: D
authors.initials: D
authors.lastname: Zagury
authors.forename: M
authors.initials: M
authors.lastname: Feldman