Naturally occurring substitutions of the human T-cell leukemia virus type 1 3' LTR influence strand-transfer reaction.

التفاصيل البيبلوغرافية
العنوان: Naturally occurring substitutions of the human T-cell leukemia virus type 1 3' LTR influence strand-transfer reaction.
المؤلفون: Leclercq, I., Mortreux, F., Rabaaoui, S., Jonsson, Cb, Wattel, E.
المساهمون: 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, We would like to thank Agnes Lanc¸on and Marie- Dominique Reynaud for assistance. This work was supported by grants from the Centre National pour la Recherche Scientifique (CNRS), the Centre Le´on Be´- rard, the Association pour la Recherche sur le Cancer (ARC), the Fondation contre la Leuce´mie, the Comite´s De´partementaux du Rhoˆne et de la Saoˆne et Loire de la Ligue Contre le Cancer, the Re´gion Rhoˆne-Alpes (programme Emergence), and the Agence Nationale pour la Recherche sur le Sida (ANRS). IL was supported by bursaries from the Ministe`re de l'Enseignement Supe´rieur et de la Recherche, FM was supported by bursaries from the Ministe`re de l'Enseignement Superieur et de la Recherche and from the Fondation pour la Recherche Medicale.
المصدر: https://hal.science/hal-00119668Test ; 2006.
بيانات النشر: HAL CCSD
سنة النشر: 2006
المجموعة: HAL Lyon 1 (University Claude Bernard Lyon 1)
مصطلحات موضوعية: Base Sequence, Human T-lymphotropic virus 1/*genetics, Humans, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Research Support, Non-U.S. Gov't, Terminal Repeat Sequences, Virus Integration, OCIS 000.1430, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
الوصف: Having isolated somatically mutated HTLV-1 3' LTR sequences from six infected individuals, the effect of these mutations on the integration process in vitro was investigated. Double-strand pre-processed HTLV-1 3' LTR ends (53-54 bp) were used in an in vitro strand-transfer reaction, together with HTLV-1 purified integrase and using a synthetic double-strand naked DNA oligonucleotide as target. Integration efficiency was measured by a fluorescent PCR assay. No significant difference in the pattern of strand transfer was observed between the distinct patients consensus sequences. For each patient, the effect of acquired somatic mutations was then assessed by comparing the strand-transfer efficiency of the mutated sequences (n=8, each harboring one to two substitutions) with that of the corresponding patient consensus sequence. Five somatic mutations or deletions at positions 7, 10, 21, 30, and 53 from the proviral 3' end did not alter the reaction efficiency. By contrast, a single G-->A transition at position 52 was found to result in 33% gain of function. Furthermore, a C-->T transition at 41 bp from the provirus 3' end decreased the reaction efficiency by 80%. This is the first study investigating the effect of naturally acquired substitutions on the strand-transfer capacity of long LTR sequences in vitro. Disproving the hitherto assumed opinion that integration specificity is restricted to the extreme boundary of the LTR end, i.e. the last 12-20 bp of the unintegrated provirus, the present results demonstrate that naturally occurred substitutions of the HTLV-1 LTR can alter significantly its strand-transfer capacity.
نوع الوثيقة: report
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/12711052; hal-00119668; https://hal.science/hal-00119668Test; PUBMED: 12711052
الإتاحة: https://hal.science/hal-00119668Test
رقم الانضمام: edsbas.9A2039B9
قاعدة البيانات: BASE