Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts.
We have investigated the molecular basis of human immunodeficiency virus type 1 (HIV-1) latency in a tissue culture model and in HIV-infected people. We show that increased levels of Tat, but not Rev, can release the proviruses from latency in U1 cells. The absence of Tat in these cells is manifested by the accumulation of promoter-proximal viral transcripts, whereas the presence of Tat correlates with increased expression of viral proteins and an increase in promoter-distal transcripts. The presence of promoter-proximal transcripts also serves as a marker for latency in humans. We observed the exclusive presence of promoter-proximal viral transcripts in peripheral mononuclear cells from the majority (10/11) of asymptomatic HIV-infected individuals examined. Activation of these cells in vitro, and viremia in vivo, correlated with a switch from promoter-proximal transcription to promoter-distal transcription. These results suggest that the control between latency and replication of HIV in vivo is at the level of transcription elongation.
Adams
M
M
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143.
Sharmeen
L
L
Kimpton
J
J
Romeo
J M
JM
Garcia
J V
JV
Peterlin
B M
BM
Groudine
M
M
Emerman
M
M
D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D015757:Genes, rev; D015756:Genes, tat; D015658:HIV Infections / Q000382:microbiology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D017735:Virus Latency; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D017931:DNA Primers; D015694:Gene Products, rev; D015696:Gene Products, tat; D012333:RNA, Messenger; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus