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

Although the use of the 5 0 UTR IRES of HIV-1 during viral infection is still questioned, several studies support the suggestion that this IRES benefits the virus during its replication in infected cells. The 5 0 UTR IRES is activated in cell extracts that were blocked in the G2/M phase of the cell cycle, a phase where cap-dependent translation is decreased (18) . The IRES-dependent translation of HIV-1 full-length mRNA could be useful to ensure viral replication when the viral protein Vpr induces G2 cell cycle arrest (41, 42) . Recently, Castello et al. (43) showed that HIV-1 protease cleaves the canonical initiation factors eIF4GI and PABP, which inhibits cap-dependent translation in HeLa extracts, but not translation of HIV-1 full-length mRNA. Stimulation of a viral IRES by viral infection has also been described for FIV whose RNA contains a dormant IRES that is activated by FIV infection and by cellular stress (24) . It is well-known that infection of HIV-1 causes oxidative and endoplasmic reticulum stresses (44) (45) (46) (47) and such stresses could influence the activity of the HIV-1 IRES.