The complexity of genome integration process in human lentivirus

Abstract

Introduction. The distribution of human lentiviral cDNA into the host genome has been studied using a linear structural approach, however such analysis is incomplete because do not consider the dynamics and topology of interphase chromatin and the gene expression networks in infected cells. Objective. To correlate using a non-linear approach the multifractality of human chromosomes, with the composition and disturbing of chromatin topology, as complex effect promote by the lentiviral cDNA integration. Methods. From 2,409 human genome sequences flanking the 5'LTR of human and simian lentiviruses obtained from GeneBank (NCBI) database, several human genomic variables were correlated with the multifractality values AvΔDq of chromosomes covering more than 98.6% of the human genome. Moreover Cytoscape v.2.63 was used to simulate the effects of viral cDNA integration on gene expression networks in macrophages. Results. The 54.21% of lentivirus cDNA integrations were registered in chromosomes with high and medium fractality; 18.14% of these cDNA integrations was exclusively located in chromosomes 16, 17, 19 and 22 corresponding to that with high multifractality values. High scores of Pearson's correlation for AvΔDq/ chromosome vs integrations/chromosome; percentage of Alu sequences were recorded. 2,770 interactions among 28 genes located closed to HIV-1 proviruses in human macrophages were recorded. cDNA integration alters the gene interaction networks in infected cells, the topological parameters of non-infected macrophage network gene was dramatically changed upon HIV-1 integration. Conclusion. Some topological changes in those regions with high frequency of cDNA viral integrations would synergistically configure local topological chromatin environments that alters the gene interaction networks in infected cells.