Author: Gendron, Karine; Ferbeyre, Gerardo; Heveker, Nikolaus; Brakier-Gingras, Léa
Title: The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element Document date: 2010_10_8
ID: qtn3ukf4_5
Snippet: In this study, we investigated the activity of the 5 0 UTR IRES of HIV-1, using site-directed mutagenesis. We also investigated the effect of various stress conditions on this IRES activity. We found that deleting an unstructured region downstream of the PBS (nt 202-217), mutating 3 nt (nt 240-242) in a 4-nt bulge in the DIS hairpin or mutating a stretch of four A (nt 302-305) in loop I downstream of the SD hairpin, decrease the IRES activity. In.....
Document: In this study, we investigated the activity of the 5 0 UTR IRES of HIV-1, using site-directed mutagenesis. We also investigated the effect of various stress conditions on this IRES activity. We found that deleting an unstructured region downstream of the PBS (nt 202-217), mutating 3 nt (nt 240-242) in a 4-nt bulge in the DIS hairpin or mutating a stretch of four A (nt 302-305) in loop I downstream of the SD hairpin, decrease the IRES activity. In contrast, deleting or mutating a stem-loop upstream of the PBS (nt 134-178) increases the IRES activity. A similar increase is observed when the activity of the wild-type IRES is assessed in cells treated with agents that induce oxidative stress. The relationship between the mutational analysis and the IRES activity is discussed. A model is proposed to account for the effect of the 134-178 stemloop on the IRES activity in relationship with the oxidative stress caused by infection with HIV-1.
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