Stochastic gene expression as a molecular switch for viral latency.

Stochastic 'noise' arises from random thermal fluctuations in the concentration of protein, RNA, or other molecules within the cell and is an unavoidable aspect of life at the single-cell level. Evidence is accumulating that this biochemical noise crucially influences cellular auto-regulatory circuits and can 'flip' genetic switches to drive probabilistic fate decisions in bacteria, viruses, cancer, and stem cells. Here, we review how stochastic gene expression in key auto-regulatory proteins can control fate determination between latency and productive replication in both phage-lambda and HIV-1. We highlight important new studies that synthetically manipulate auto-regulatory circuitry and noise, to bias HIV-1's ability to enter proviral latency. We argue that an appreciation of noise in gene expression may shed light on the mystery of animal virus latency and that strategies to manipulate noise may have impact on anti-viral therapeutics.