Intragenic transcriptional cis-activation of the human immunodeficiency virus 1 does not result in allele-specific inhibition of the endogenous gene

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.Retroviruses, such as human immunodeficiency virus type 1 (HIV-1) require reverse transcription and integration into host chromatin to establish a provirus as an obligatory replication step. The choice of the integration site is a crucial intermediate of the virus life cycle. The chromatin context determines the efficiency of viral transcription and is involved in the establishment of post-integrative latency that is the major obstacle to HIV-1 eradication with current antiviral therapies [1-3]. In addition, insertion of a provirus in the human genome can cause several adverse effects [4]. For example, insertion of the retrovirus close to a proto-oncogene may induce transformation of the cell. Gene therapy approaches suffer most from these effects and recently it has been demonstrated that the activation of an oncogene caused transformation in several children treated with a therapeutic retroviral vector [5]. In principle, insertion of an ectopic transcription unit within a gene may also result either in disruption of exonic sequences, introd