Myeloid dendritic cells induce HIV-1 latency in non-proliferating CD4+ T cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Latently infected resting CD4(+) T cells represent a significant obstacle to achieving a cure for HIV.
• Understanding the mechanisms of HIV latency establishment, maintenance, and reversal is essential for developing effective elimination strategies.

Purpose of the Study:

• To investigate the role of myeloid dendritic cells (mDCs) in the establishment of HIV latency in CD4(+) T cells.
• To determine the contribution of cell-to-cell contact versus soluble factors in mediating HIV latency.

Main Methods:

• Co-culture of resting CD4(+) T cells with syngeneic mDCs.
• Manipulation of cell-to-cell contact and clustering during co-culture.
• Analysis of HIV DNA integration and latent infection frequency.
• Gene expression profiling of infected CD4(+) T cells.

Main Results:

• Co-culture with mDCs significantly increased HIV DNA integration and latent infection in non-proliferating memory CD4(+) T cells.
• Prevention or minimization of cell-to-cell contact abrogated or reduced latency, respectively.
• Supernatants from mDC-T cell co-cultures did not induce latency, highlighting the importance of direct contact.
• Gene expression changes in latently infected cells indicated altered cellular activation and interferon pathways, with down-regulation of NF-κB and cell cycle genes.

Conclusions:

• Myeloid dendritic cells play a critical role in establishing HIV latency in resting memory CD4(+) T cells.
• The process is primarily mediated by cell-cell contact and associated signaling, not soluble factors.
• Targeting DC-T cell interactions could be a novel strategy to combat HIV latency.