HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to...

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Latent HIV infection establishes a reservoir, hindering viral eradication.
• Current latency biomarkers identify only a portion of the HIV reservoir.
• HIV latency can arise in both dividing and resting cells.

Purpose of the Study:

• To investigate transcriptomic changes during early HIV infection in cells with varying proliferative responses.
• To understand how T cell receptor (TCR) signaling influences HIV latency establishment.
• To identify potential cellular biomarkers for latent HIV infection based on early cellular states.

Main Methods:

• Monitoring cell proliferation using carboxyfluorescein diacetate succinimidyl ester (CFSE).
• Performing single-cell RNA sequencing on cells with different division histories post-HIV infection.
• Analyzing transcriptomic remodeling induced by HIV infection and TCR stimulation.

Main Results:

• HIV infection induced transcriptional changes, some independent of cell division number.
• Distinct transcriptional responses were observed in different cell subsets.
• Early gene expression changes correlated with known markers of latently infected cells.

Conclusions:

• The cellular proliferative state at the time of HIV infection influences early gene expression.
• These early transcriptional changes may serve as predictive biomarkers for HIV latency.
• Understanding these early events is key to developing strategies for latent HIV reservoir targeting.