Lack of correlation between basal expression levels and susceptibility to transcriptional shutdown among single-gene murine leukemia virus vector proviruses.
Integrated retroviruses or retroviral vectors may be transcriptionally inactive although their promoter-enhancer regions are able to direct transcription in the host cell. We have used single-gene retroviral vectors with a long terminal repeat-directed neo marker gene to determine if the level of transcription relates to the susceptibility of a provirus to inactivation. We used two isogenic vectors, carrying long terminal repeats with a strong and a weak transcriptional enhancer derived from SL3-3 and Akv murine leukemia viruses, respectively. Nonselected cell clones of the murine lymphoid cell line L691 with single integrated vector proviruses exhibiting a 20-fold range of initial expression levels were studied. The basal expression level of a given cell clone with a single provirus did not show any pattern of correlation with the long-term stability of expression, as monitored for periods up to 150 days. Our results thus indicate that the inactivation mechanism operates independently of the initial transcriptional activity of the provirus.
Duch
M
M
Department of Molecular Biology, University of Aarhus, Denmark.
Paludan
K
K
Jørgensen
P
P
Pedersen
F S
FS
D002460:Cell Line; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D009052:Leukemia Virus, Murine / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic
D012333:RNA, Messenger