 Viral expression of Nef induces numerous changes within the infected cell including the modulation of protein cell surface expression, cytoskeletal remodeling, and signal transduction.Since the activation state of the infected cell plays an important role in the success rate of HIV-1 infection, it is important that resting T-cells be primed to respond to T-cell receptor (TCR) stimuli.HIV-1 Nef lowers the threshold for activation of CD4+ lymphocytes, but is not sufficient to cause activation in the absence of exogenous stimuli.