Do retroviruses preferentially integrate within highly plastic regions of the human genome?
Whether retroviral integration is a phenomenon specific to properties of the surrounding genomic region is a widely debated question. In this paper we attempt to enlight the involvement of genomic regions prone to DNA double strand breaks in such process, as well as the more general concept of genome plasticity concerning repair, recombination, transposition events. While performing a differential display analysis of the promonocytic cell line U937 and clone U42 HIV infected counterpart, we found, out of about 15 highly dysregulated genes, expected according to our previous proteomic analysis, two dysregulated cellular transcripts that are shown in the present study to colocalize on band 22q11. The LB14 transcript maps within the DiGeorge critical region. Whereas the AG46 transcript encodes the immunoglobulin-lambda like polypeptide 1 (IGLL1) 4.7Mb apart from LB14. The 22q11 band is remarkable for its high plasticity involving DNA double strand breaks, that may lead to translocations, large deletions, and immunoglobulin rearrangements, frequently observed in this region. We suggest that provirus integration preferentially occurs in such genomic regions and that the subsequent insertional mutagenesis leads to the present observations. Finally, we stress out the possibility that the small size of chromosome 22 is associated with this physical property of the genome.
Guinet
E
E
CNRS UPR 9045, IRC, Villejuif, France.
Mimaud
V
V
Rossignol
P
P
Hameau
L
L
Benboudjema
L
L
Jasmin
C
C
Tovey
M G
MG
Bélec
L
L
Lang
M-C
MC
D002892:Chromosomes, Human, Pair 22; D004249:DNA Damage; D020869:Gene Expression Profiling; D015894:Genome, Human; D006678:HIV / Q000472:pathogenicity; D006801:Humans; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells; D016662:Virus Integration