Intragenic transcriptional cis-activation of the human immunodeficiency virus 1 does not result in allele-specific inhibition of the endogenous gene
Open Access
- 4 November 2008
- journal article
- research article
- Published by Springer Nature in Retrovirology
- Vol. 5 (1) , 1-15
- https://doi.org/10.1186/1742-4690-5-98
Abstract
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. 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. 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.Keywords
This publication has 50 references indexed in Scilit:
- An Ungracious Host for an Unwelcome GuestCell Host & Microbe, 2008
- Orientation-Dependent Regulation of Integrated HIV-1 Expression by Host Gene Transcriptional ReadthroughCell Host & Microbe, 2008
- Integration Site Selection by Retroviral Vectors: Molecular Mechanism and Clinical ConsequencesHuman Gene Therapy, 2008
- The transcriptional cycle of HIV-1 in real-time and live cellsThe Journal of cell biology, 2007
- HIV integration site selection: Analysis by massively parallel pyrosequencing reveals association with epigenetic modificationsGenome Research, 2007
- Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latencyThe EMBO Journal, 2007
- Homologous gene sequences mediate transcription-domain formationJournal of Cell Science, 2006
- Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site PreferencesPLoS Biology, 2004
- LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1Science, 2003
- HIV-1 Integration in the Human Genome Favors Active Genes and Local HotspotsCell, 2002