[Clonal expansion and genomic characterization of the human T-cell lymphotropic virus type I during the integration process in adult T-cell leukemia/lymphoma].
BACKGROUND
Although the integration of human T-cell lymphotropic virus type I into the T-cells is not a random process, the mechanistic details are not understood.


OBJECTIVE
The characteristics of the flanking host chromatin were evaluated at the integration sites in adult T-cell leukaemia/lymphoma (ATLL) patients infected with the virus.


METHODS
From seven leukemic Colombian patients positive for the human T-cell lymphotropic virus type I (HTLV-I), lymphocyte DNA samples were extracted and amplified by inverse polymerase chain reaction (IPCR). Clonal expansion and human genome nucleotide composition in an extension of 50 bp was determined. To establish the characteristics of the human genome flanking provirus, 61 IPCR sequences from Colombian and Japanese ATLL patients, were analyzed in silico to obtain insights about the genomic structure, functions and nature of associated chromatin.


RESULTS
The clonal expansion of cell clones was predominantly oligoclonal. From 61 IPCR sequences, 155 alignments with homology higher than 95% (e-value < 0.05) were screened. Seventy-five percent of those sequences corresponded to non coding elements that include repetitive and non-repetitive DNA. Fifty percent of the proviral integrations were associated with chromosomes of A and B groups. Viral DNA integration tended to favor exons of genes that replicated early, controlled the cell cycle, or were involved in signal transduction.


CONCLUSIONS
The results indicated that HTLV-I integration was preferentially directed towards genomic environments with high C:G content, and toward genes that replicate early, regulate cell cycle or involved with signal transduction.
Salcedo-Cifuentes
Mercedes
M
Laboratorio de Biología Molecular y Patogénesis, Departamento de Ciencias Fisiológicas, Facultad de Salud, Universidad del Valle, Cali, Colombia.
Cabrera
Jesús
J
Cuesta-Astroz
Yesid
Y
Carrasca
Edwin
E
Eizuru
Yoshito
Y
Domínguez
Martha C
MC
Sánchez
Adalberto
A
García-Vallejo
Felipe
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001482:Base Composition; D002472:Cell Transformation, Viral / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000821:virology; D004261:DNA Replication / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D018816:Genes, cdc; D016355:Genes, pX; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics* / Q000302:isolation & purification; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D016662:Virus Integration / Q000235:genetics*; D055815:Young Adult
D004273:DNA, Neoplasm; D004279:DNA, Viral