Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation

Academic Article

Abstract

  • Previous studies have shown that human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. Herein, we show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell death. Levels of active Bak are higher in HIV-infected T cells that express Casp8p41. Conversely, targeted mutations in the Bak-interacting domain diminish Bak binding and Casp8p41-mediated cell death. Similar mutations in procaspase 8 impair the ability of HIV to kill infected T cells. These observations support a novel paradigm in which HIV converts a normal cellular constituent into a direct activator that functions like a BH3-only protein.
  • Digital Object Identifier (doi)

    Author List

  • Sainski AM; Dai H; Natesampillai S; Pang YP; Bren GD; Cummins NW; Correia C; Meng XW; Tarara JE; Ramirez-Alvarado M
  • Start Page

  • 867
  • End Page

  • 876
  • Volume

  • 206
  • Issue

  • 7