  Many viruses have the cunning ability to enter a hibernative or off state,
termed latency or lysogeny. When in a latent state, the virus is unable to
replicate, and its gene expression program is largely shut down. This facility
for lying dormant typically ensures lifelong persistence of the virus in the
host; it is also a particularly problematic obstacle in the treatment of HIV.
For most viruses, the molecular regulation of entry into latency is not
completely understood, but it is believed that viral gene expression must be
deactivated in some way. In this study, we introduce a new regulatory motif,
the feedback resistor, that enables a genetic circuit to shut off without the
need for an active repressor molecule. We first show that many animal viruses
might encode feedback resistors in their regulatory circuits. Then, by using a
combination of mathematical theory and single-cell real-time imaging
experiments, we show that a feedback resistor in the HIV Tat transcriptional
circuit likely allows the HIV virus to enter into latency. We postulate that
feedback resistors may give increased stability and control in the complex
noisy signaling environment of the cell.
