Table 3 Models addressing the effects of MME reconfiguration of HIV gene-expression
From: Mathematical modeling and mechanisms of HIV latency for personalized anti latency therapies
Study | Aims | Data | Results | |
|---|---|---|---|---|
Latency Reversal | A. K. Chavali et al.30 | Understand the factors and mechanisms related to the MME that modulate HIV gene-expression noise, eventually inducing latency-reversal upon induced MME reconfiguration. | LTR-driven GFP expression of 105 HIV-infected Jurkat T-cell clones upon Aza and TNF stimulation. | (i) The two- and three-state LTR models captures the mechanisms by which basal HIV gene-expression may induce latency-reversal; (ii) The Fano-factor proves to be a useful noise metric to compare models’ prediction. (iii) The three-state LTR model well captures changes in basal viral activity after LRAs-driven MMEs reconfigurations. |
V. G. Wong et al.31 | Understand the factors and mechanisms related to the MME that modulate HIV gene-expression noise, eventually inducing latency-reversal upon induced MME reconfiguration. | time-resolved, single-cell transcriptional data over multiple IS upon NF-κB stimulation. | (i) The TNF-induced increase of transcription variability at the provirus level is higher than its mean HIV transcripts count; (ii) TNF-induced NF-kb activation correlates with latency-reversal. (iii) NF-kb levels, must be combined with chromatin structure and RNAPII regulation to explain the observed provirus-specific variability | |
Y. Cao et al.34 | (i) Identify targetable key reactions critical for Tat-amplification to shorten stochastic delays and speed-up latency reversal; (ii) Build HIV gene-expression model for in-silico LRAs efficacy testing | Parameters estimates taken from the literature | (i) The Tat circuit exhibits a bimodal probability landscape, where a peak is associated with latency, and another with the active fate; (ii) Enhancing Tat acetylation may increase Tat and viral production; (iii) Increasing the binding affinity between the LTR and Tat may induce an easier transition to the viral-phase; (i) Adopting a modeling framework is a valid approach to search and discovery potentially effective therapeutic strategies and compounds |
