Death by Firestorm: Why Bystander CD4 Cells Die During HIV Infection

Although the death of productively HIV-infected T cells is known to occur through apoptosis, the overwhelming demise of quiescent “bystander” CD4 cells, which reside mostly in lymphoid tissues, remains unexplained. The cause of heightened inflammation in the setting of HIV infection is also not well understood.

Now, using fresh human tonsillar tissue, researchers in San Francisco have demonstrated that the way lymphoid CD4 cells die depends on the manner in which HIV infects them. They found that CD4 cells must be activated to permit productive HIV infection. HIV can also infect latent, nonpermissive CD4 cells, but the ill-suited cellular environment causes the HIV life cycle to be halted during reverse transcription. A small proportion of l…