Systems biology applications to study mechanisms of human immunodeficiency virus latency and reactivation

Eradication of human immunodeficiency virus (HIV) in infected individuals is currently not possible because of the presence of the persistent cellular reservoir of latent infection. The identification of HIV latency biomarkers and a better understanding of the molecular mechanisms contributing to regulation of HIV expression might provide essential tools to eliminate these latently infected cells. This review aims at summarizing gene expression profiling and systems biology applications to studies of HIV latency and eradication. Studies comparing gene expression in latently infected and uninfected cells identify candidate latency biomarkers and novel mechanisms of latency control. Studies that profiled gene expression changes induced by existing latency reversing agents (LRAs) highlight uniting themes driving HIV reactivation and novel mechanisms that contribute to regulation of HIV expression by different LRAs. Among the reviewed gene expression studies, the common approaches included identification of differentially expressed genes and gene functional category assessment. Integration of transcriptomic data with other biological data types is presently scarce, and the field would benefit from increased adoption of these methods in future studies. In addition, designing prospective studies that use the same methods of data acquisition and statistical analyses will facilitate a more reliable REVIEW 6