Biopolymers and cell. 2000; 16 (6): 547 - 558

Compositional specificity of human T-cell leukemia virus type I and human immunodeficiency virus type 1 integration into the human genome

L. O. Tsyba, S. V. Zoubak, N. Tryapitsina-Guley, G. Bernardi, A. V. Rynditch

Localization of HTLV-1 (human T-cell leukemia virus type I) and H1V-1 (human immunodeficiency virus type 1) proviral sequences in compositional compartments of genomes of patients with different manifestation of infection have been studied by a new technique of centrifugation in shallow CsCl gradients with two buoyant density markers. The major peaks of distribution of GC-rich HTLV-I sequences in genomes of 18 patients were centered at GC-rich (> 44 % GC) regions of the human genome which usually account 30 % of the genome and contain transcriptionally active HTLV-I sequences (Zoubak et al. (1994) Gene 143, 155—163). In the case of patients with T-cell leukemia (ATL) viral sequences were not found below 44 % GC. Patients with TSP/HAM and asymptomatic carriers had a broader and multimodal distribution of HTLV-I (at 38—54,8 % GC) with minor peaks in GC-poorer regions. GC-poor HIV-1 proviruses were found in both GC-poor and GC-rich compartments of genomes of 27 patients with different levels of virus production. More intense peaks were centered at GC-rich regions for the patients with lower virus load. These results have revealed that the distribution of integrated proviruses in vivo is nonuniform in the compositional compartments of cell genome and broader than in vitro.