Intragenic transcriptional cis-activation of the human immunodeficiency virus 1 does not result in allele-specific inhibition of the endogenous gene.
BACKGROUND
The human immunodeficiency virus type 1 (HIV-1) favors integration in active genes of host chromatin. It is believed that transcriptional interference of the viral promoter over the endogenous gene or vice versa might occur with implications in HIV-1 post-integrative transcriptional latency.


RESULTS
In this work a cell line has been transduced with a HIV-based vector and selected for Tat-inducible expression. These cells were found to carry a single silent integration in sense orientation within the second intron of the HMBOX1 gene. The HIV-1 Tat transactivator induced the viral LTR and repressed HMBOX1 expression independently of vector integration. Instead, single-cell quantitative in situ hybridization revealed that allele-specific transcription of HMBOX1 carrying the integrated provirus was not affected by the transactivation of the viral LTR in cis.


CONCLUSIONS
A major observation of the work is that the HIV-1 genome has inserted in genes that are also repressed by Tat and this could be an advantage for the virus during transcriptional reactivation. In addition, it has also been observed that transcription of the provirus and of the endogenous gene in which it is integrated may coexist at the same time in the same genomic location.
De Marco
Alex
A
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. marcello@icgeb.org
Biancotto
Chiara
C
Knezevich
Anna
A
Maiuri
Paolo
P
Vardabasso
Chiara
C
Marcello
Alessandro
A
D000483:Alleles; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012313:RNA / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D014158:Transcription, Genetic; D016662:Virus Integration
C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; D012367:RNA, Viral; D012313:RNA