Targeted bacteriophage T4 nanoparticles reverse HIV-1 latency in human T cell line models.

Area of Science:

• Immunology
• Virology
• Nanotechnology

Background:

• The latent HIV-1 reservoir in CD4+ T cells is a major obstacle to viral eradication.
• Targeted reactivation of this reservoir is a key strategy for achieving an HIV-1 cure.

Purpose of the Study:

• To investigate if CD4-targeted bacteriophage T4 capsid nanoparticles can reactivate HIV-1 latency.
• To explore the potential of these nanoparticles for HIV-1 cure and targeted T cell therapies.

Main Methods:

• Engineered bacteriophage T4 capsid nanoparticles displaying CD4-binding domains or HIV-1 gp140 envelope trimers.
• Exposure of J-Lat T cell model and primary human PBMCs to the nanoparticles.
• Analysis of T cell activation, HIV-1 proviral transcription, and viral protein production.

Main Results:

• Nanoparticles activated CD4+ T cells and reversed HIV-1 latency in model and primary cells.
• Activation was specific to CD4+ T cells, avoiding global T cell activation.
• Latency reversal occurred independently of classical PKC/NFAT pathways and did not induce cytokine storm.

Conclusions:

• Engineered bacteriophages can effectively reactivate latent HIV-1.
• This strategy offers a novel approach for HIV-1 cure by targeting the viral reservoir.
• The method demonstrates potential for targeted T cell therapies without adverse immune responses.