Spatial technologies to evaluate the HIV-1 reservoir and its microenvironment in the lymph node

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• The persistent HIV-1 reservoir, containing replication-competent proviruses, is a primary obstacle to curing HIV-1.
• HIV-1 reservoir cells evade immune responses and antiretroviral therapy (ART).
• CD4+ T cells are key targets, with memory T follicular helper cells in B cell follicles harboring provirus, contributing to viral rebound after ART cessation.

Purpose of the Study:

• To investigate the role of the B cell follicle microenvironment in protecting HIV-1 reservoir cells.
• To explore cell-to-cell interactions and trafficking within and from lymph node follicles.
• To identify potential targets for HIV-1 cure strategies by understanding reservoir dynamics.

Main Methods:

• Utilizing a spatiotemporal approach.
• Integrating genomics, transcriptomics, and proteomics.
• Analyzing HIV-1 reservoir and neighboring cells within lymph nodes.

Main Results:

• HIV-1 reservoir cells are found in memory T follicular helper cells within lymph node B cell follicles.
• The germinal center environment may offer immune privilege, protecting infected cells.
• Proviral DNA in lymph nodes and blood suggests inter-compartmental trafficking.

Conclusions:

• The B cell follicle's unique microenvironment is a critical factor in HIV-1 persistence.
• Further research into lymph node follicle dynamics is essential for advancing HIV-1 cure strategies.
• Integrated multi-omics approaches hold promise for dissecting the HIV-1 reservoir.