The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element

Gendron, Karine; Ferbeyre, Gerardo; Heveker, Nikolaus; Brakier-Gingras, Léa

In conclusion, our results suggest that the control of the HIV-1 5 0 UTR IRES activity is a complex event that likely combines conformational changes and the effect of cellular repressors and activators that bind to this IRES. Our results identified IRENE, a stem-loop that could play a role in the activation of this IRES upon viral infection in response to oxidative stress. More work is needed to understand the mechanism of stimulation of HIV-1 IRES by oxidative stress via IRENE and the regulation of this IRES during the virus replication cycle. The IRES-dependent translation of HIV-1 full-length mRNA must be tightly regulated during viral infection so as to favor viral replication. It will be important to characterize when this IRES is activated and utilized during the virus replication cycle and to identify the proteins which are involved in this utilization.