Possible mechanisms by which Vif may modulate the in vivo equilibrium of p-TEFb. (A) p-TEFb exists in vivo in either a kinase-active form (p-TEFb-Brd4 complex) or a kinase-inactive form (p-TEFb-HEXIM1-7SK RNA complex). Brd4 and HEXIM1 act as positive and negative regulators, respectively, of the complex to reciprocally affect the functional equilibrium of p-TEFb. The appropriate equilibrium of p-TEFb is known to be important for growth and differentiation. (B) Postulated mechanisms by which Vif could alter the equilibrium of p-TEFb. Hypothesis A: Vif shifts the equilibrium of p-TEFb away from the inactive, anti-growth state and toward the active, pro-growth state by releasing p-TEFb from negative regulation by the HEXIM1-7SK RNA complex. Hypothesis B: Vif interacts directly with Brd4 and Cdk9 to promote the formation of the active, pro-growth state of p-TEFb.