CELLULAR LATENCY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALSWITH HIGH CD4 LEVELS CAN BE DETECTED BY THE PRESENCE OF PROMOTER-PROXIMAL TRANSCRIPTS

We have investigated the molecular basis of human immunodeficiency vir us type 1 (HIV-1) latency in a tissue culture model and in HIV-infecte d people. We show that increased levels of Tat, but not Rev, can relea se the proviruses from latency in U1 cells. The absence of Tat in thes e cells is manifested by the accumulation of promoter-proximal viral t ranscripts, whereas the presence of Tat correlates with increased expr ession of viral proteins and an increase in promoter-distal transcript s. The presence of promoter-proximal transcripts also serves as a mark er for latency in humans. We observed the exclusive presence of promot er-proximal viral transcripts ire peripheral mononuclear cells from th e majority (10/11) of asymptomatic HIV-infected individuals examined. Activation of these cells in vitro, and viremia in vivo, correlated wi th a switch from promoter-proximal transcription to promoter-distal tr anscription. These results suggest that the control between latency an d replication of HIV in vivo is at the level of transcription elongati on.