CD4/CXCR4-mediated cell death in AIDS

Is HIV infection a TNF receptor signalling-driven disease?

“…In addition, HIV-1 gp120, via interaction with CD4, activates uninfected CD4 + T cells, resulting in CD4 + T cell priming, and renders them susceptible to TNF-mediated apoptosis [42]. Furthermore, the binding of a cell-associated gp120 molecule to CXCR4 induces mitochondrial transmembrane depolarization; cytochrome C release from the mitochondria to the cytosol; and, ultimately, activation of downstream caspases, resulting in T cell apoptosis [43,44]. CD8 + T cell apoptosis in HIV infection is observed at the onset of AIDS in the context of high TNF expression [5,45,46], and it is triggered via interaction of HIV-1 gp120 with CXCR4 and via contacts between membrane-bound TNF on macrophages and TNFR2 on CD8 + T cells [5,45].…”