HIV-1 release requires Nef-induced caspase activation

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• HIV infection is currently incurable, with no therapies targeting viral release.
• Current HIV cure strategies focus on eliminating latent reservoirs via T cell apoptosis ('kick and kill').

Purpose of the Study:

• To investigate the mechanism of HIV viral release.
• To determine the role of caspases and CD62L in HIV release.
• To evaluate the implications of targeting T cell apoptosis for HIV cure.

Main Methods:

• Analysis of HIV viral release from infected CD4 T cells.
• Investigation of caspase activation and CD62L shedding.
• Transcriptomic analysis of HIV-infected cells.
• Inhibition of caspases activation.

Main Results:

• HIV release is not spontaneous but requires caspases activation and CD62L shedding.
• Blocking caspases leads to virion tethering by CD62L and deficient viral release.
• HIV release from patient-derived cells and experimental infections depends on caspase activation.
• HIV accessory gene Nef contributes to caspase activation.

Conclusions:

• HIV release from cellular reservoirs is linked to apoptotic shedding of CD62L, dependent on caspases.
• Targeting T cell apoptosis ('kick and kill') may inadvertently promote HIV release.
• Inhibiting caspases activation offers a potential strategy to block viral reservoir release.