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A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells
Ramesh Ramji1, Victor C Wong2, Arvind K Chavali1
1Department of Biomedical Engineering, Yale University, New Haven, CT 06511.
Summary
Researchers developed a microfluidic device to study HIV activation in single cells. This method reveals drug-specific patterns in viral activation, crucial for optimizing HIV latency reversal therapies.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Cell-to-cell variability in drug response is critical for therapeutic efficacy.
- Optimizing latency reversing agents (LRAs) for HIV cure strategies requires understanding heterogeneous viral activation dynamics.
Purpose of the Study:
- To evaluate heterogeneity in latent HIV activation across various LRAs.
- To develop a method for tracking drug-induced response dynamics in single suspension cells.
Main Methods:
- Utilized a latent HIV-GFP reporter virus in Jurkat T cells.
- Designed a passive-flow microfluidic device for single-cell capture and live-cell imaging.
- Quantified viral activation heterogeneity stimulated by transcription factor (TF) activators and histone deacetylase (HDAC) inhibitors.
Main Results:
- TF activators showed faster onset and production rates; HDAC inhibitors had uniform onset but heterogeneous production rates.
- Onset time and production rate independently predict total HIV activation.
- Onset time and production rate are not correlated within individual cells.
Conclusions:
- Drug-specific patterns of noisy HIV activation dynamics were identified.
- These findings may inform the design of effective activate-and-kill HIV treatment regimens.
- The microfluidic device enables novel insights into dynamic single-cell responses.

