Dynamics of the Gene Regulatory Network of HIV-1 and the Role of Viral Non-coding RNAs on Latency Reversion.

ABSTRACT: The use of latency reversing agents (LRAs) is currently a promising approach to eliminate latent reservoirs of HIV-1. However, this strategy has not been successful in vivo. It has been proposed that cellular post-transcriptional mechanisms are implicated in the underperformance of LRAs, but it is not clear whether proviral regulatory elements like viral non-coding RNAs (vncRNAs) are also implicated. In order to visualize the complexity of the HIV-1 gene expression, we used experimental data to construct a gene regulatory network (GRN) of latent proviruses in resting CD4+ T cells. We then analyzed the dynamics of this GRN using Boolean and continuous mathematical models. Our simulations predict that vncRNAs are able to counteract the activity of LRAs, which may explain the failure o

SUBMITTER: Bensussen A 

PROVIDER: S-EPMC6172855 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature