HIV-1 latency due to the site of proviral integration.
Cell lines that are nonproductively infected with human immunodeficiency virus type 1 (HIV-1), such as the T-lymphocyte ACH2 clone, have been proposed to represent in vitro models of proviral latency. We have previously shown that such cells exhibit an aberrant pattern of viral RNA expression, with a large excess of fully spliced viral RNAs. Here, by superinfecting the ACH2 cells with a second HIV-1 virus, we demonstrate the primary mechanism of HIV-1 proviral latency in this cell line. In the dually infected cells, the exogenous virus was transcribed at high levels. However, expression from the provirus originally present in the ACH2 cells was not quantitatively increased. Still, its RNA production was shifted from a blocked early-stage to a fully productive pattern. This was interpreted to be a consequence of the high levels of Rev produced by the exogenous virus, acting in trans to promote the cytoplasmic export of all incompletely spliced viral mRNAs made in the cells. Comparable numbers of copies of each provirus were present in the dually infected cells, and both viruses grew equally well, once passed onto fresh cells. These results indicate that the low levels of transcriptional activity of the HIV-1 virus present in ACH2 cells are secondary to specific characteristics of the region of the cellular genome in which the proviral DNA is integrated.
Infectious Disease Laboratory, Salk Institute, La Jolla, California 92037-1099.
B J
BJ
Winslow
R J
RJ
Pomerantz
O
O
Bagasra
D
D
Trono
D001483:Base Sequence; D002478:Cells, Cultured; D015694:Gene Products, rev / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000254:growth & development*; D012367:RNA, Viral / Q000096:biosynthesis; D015163:Superinfection; D014158:Transcription, Genetic; D016662:Virus Integration; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus