Single-Molecule Threshold of HIV Fate Decision

Abstract

During early infection, the HIV virus makes a key decision between two states: lytic and lysogenic fate. Deterministic bistability requires combination of positive feedback and ultrasensitivity. Although HIV circuity includes positive feedback activation of the Tat transactivator, it lacks ultrasensitivity. How does the HIV circuit allow for multiple fates without ultrasensitivity? A new article suggests that HIV bistability is a result of a transient threshold that allows the kinetic trapping of the inactive state. Interestingly, the model shows that the transient threshold is a result of a single molecule threshold that occurs when the promoter toggles between inactive and active states.