Naturally occurring substitutions of the human T-cell leukemia virus type 1 3' LTR influence strand-transfer reaction. - Archive ouverte HAL
Pré-Publication, Document De Travail Année : 2006

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

Résumé

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.
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Dates et versions

hal-00119668 , version 1 (11-12-2006)

Identifiants

  • HAL Id : hal-00119668 , version 1
  • PUBMED : 12711052

Citer

I. Leclercq, F. Mortreux, S. Rabaaoui, Cb Jonsson, E. Wattel. Naturally occurring substitutions of the human T-cell leukemia virus type 1 3' LTR influence strand-transfer reaction.. 2006. ⟨hal-00119668⟩
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