De Marco Alex, Biancotto Chiara, Knezevich Anna, Maiuri Paolo, Vardabasso Chiara, Marcello Alessandro
Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Retrovirology. 2008 Nov 4;5:98. doi: 10.1186/1742-4690-5-98.
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.
1型人类免疫缺陷病毒(HIV-1)倾向于整合到宿主染色质的活性基因中。据信,病毒启动子对内源基因的转录干扰或反之亦然,可能会对HIV-1整合后转录潜伏期产生影响。
在这项工作中,用基于HIV的载体转导了一个细胞系,并选择用于Tat诱导表达。发现这些细胞在HMBOX1基因的第二个内含子内以正义方向携带单个沉默整合。HIV-1 Tat反式激活因子诱导病毒长末端重复序列(LTR)并独立于载体整合抑制HMBOX1表达。相反,单细胞定量原位杂交显示,携带整合前病毒的HMBOX1的等位基因特异性转录不受病毒LTR顺式反式激活的影响。
这项工作的一个主要观察结果是,HIV-1基因组已插入到也被Tat抑制的基因中,这在转录重新激活期间可能对病毒有利。此外,还观察到前病毒及其整合到的内源基因的转录可能在同一基因组位置同时共存。