Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Immune system responsiveness changes with age and biological sex.
• CD4+ T cells from women with HIV show reduced viral replication compared to men's.

Purpose of the Study:

• To investigate the in vitro effect of sex and age on HIV permissiveness in primary CD4+ T cells.
• To identify cellular markers associated with differential HIV susceptibility.

Main Methods:

• Primary CD4+ T cells from 20 donors were infected with HIV-based vectors.
• Cells were analyzed over six days for permissiveness, surface marker expression, and transcriptomics.
• Single-cell RNA sequencing was used to assess cell population heterogeneity.

Main Results:

• HIV permissiveness increased between 24-72 hours post-stimulation.
• Cells from males and donors over 50 years old showed increased HIV susceptibility.
• Higher frequencies of activation marker CD69 and immune checkpoint inhibitors (PD-1, CTLA-4) correlated with HIV expression.
• Transcriptomic analysis revealed enriched activation and cell cycle gene sets in male and older female cells.

Conclusions:

• Male sex and older age are associated with increased CD4+ T cell permissiveness to HIV in vitro.
• Activation markers and immune checkpoints play a role in differential HIV susceptibility.
• These findings are crucial for developing targeted HIV cure strategies, especially concerning latency reactivation.