التفاصيل البيبلوغرافية
| العنوان: |
Basis of HTLV type 1 target site selection. |
| المؤلفون: |
Leclercq, I., Mortreux, F., Gabet, As, Jonsson, Cb, Wattel, E. |
| المساهمون: |
Génétique moléculaire et approches thérapeutiques des hémopathies malignes, IRCL-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Molecular and Vascular Biology, Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven), Virologie et pathogenèse virale (VPV), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), New Mexico State University, These studies were supported by grants from the Association pour la Recherche sur le Cancer (ARC), from the Ligue Nationale contre le Cancer (Comité Pas de Calais), and from the Fondation Contre la Leucémie. I.L. and F.M. were supported by bursaries from the Ministère de l'Enseignement Supérieur et de la Recherche and from the ARC. A.S.G. was supported by a bursary from the Centre Léon Bérard. We thank Pr. Wattre and collaborators, who kindly welcomed us in their laboratories for DNA extraction, digestion, ligation, and PCR. We also thank Marie-Dominique Reynaud for assistance. |
| المصدر: |
https://hal.science/hal-00116700Test ; 2006. |
| بيانات النشر: |
HAL CCSD |
| سنة النشر: |
2006 |
| المجموعة: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: |
Base Sequence, DNA/genetics, HIV Integrase/genetics/metabolism, HIV-1/genetics, HTLV-I Infections/*virology, Human T-lymphotropic virus 1/*genetics/pathogenicity/physiology, Humans, Integrases/genetics/metabolism, Research Support, Non-U.S. Gov't, Terminal Repeat Sequences/genetics, Virus Integration/*genetics, OCIS 000.1430, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology |
| الوصف: |
Sequencing integration sites from >/=200 proviruses isolated from infected individuals revealed that HTLV-1 integration is not random at the level of the nucleotide sequence. The virus was found to integrate in A/T-rich regions with a weak consensus sequence at positions within and without the hexameric repeat generated during integration. These features were not associated with a preference for integration near active regions or repeat elements of the host chromosomes. However, about 6% of HTLV-1 proviruses were found to be integrated into transcription units, suggesting that in some cells, HTLV-1 integration may alter gene expression in vivo. Therefore, the target choice in vivo seems to be determined by local features rather than by the accessibility of specific regions. This led us subsequently to analyze the role of the DNA structure in HTLV-1 integration in vitro. Double-strand HTLV-1 or HIV-1 3' LTR extremities were used as substrates for in vitro strand transfer reactions using highly purified HTLV-1 and HIV-1 integrases (INs) expressed in Escherichia coli, and two synthetic naked 50-bp double-strand DNA molecules harboring different structures were used as targets. A fluorometric quantitative analysis of integration products was designed to assess the reaction efficiency for both target sequences. As suggested for HTLV-1 in vivo (present results), and, as previously described for other retroviruses in vitro, the structure of the target was found to greatly influence the site and the efficiency of integration. Both HIV-1 and HTLV-1 INs underwent the same target structural constraint, i.e., a strong preference for curved DNA. Altogether these results indicate that if most or all the regions of the genome appear to be accessible to HTLV-1 integration, local DNA curvature seems to confer a kinetic advantage for both in vitro and in vivo HTLV-1 integration. |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
info:eu-repo/semantics/altIdentifier/pmid/11080806; hal-00116700; https://hal.science/hal-00116700Test; PUBMED: 11080806 |
| الإتاحة: |
https://hal.science/hal-00116700Test |
| رقم الانضمام: |
edsbas.7D6EACB8 |
| قاعدة البيانات: |
BASE |
