Role of RNA helicases in HIV-1 replication

Jeang, Kuan-Teh; Yedavalli, Venkat

New evidence now suggests that RNA helicases are also co-factors for Rev-directed export of HIV-1 mRNAs (58) . In its role of transporting unspliced and incompletely spliced viral RNAs from the nucleus, Rev directly interacts with nuclear export receptor CRM1 (59, 60) , and CRM1 is required for Rev-mediated export of HIV RNAs (59, 61, 62) . A recent report provides data that an RNA helicase, DDX3, is an additional player in the Rev-CRM1-RRE complex (12) . Thus, it was shown that DDX3 over-expression enhanced Revdependent, but not other export, pathway; and that DDX3 is a nucleo-cytoplasmic shuttling protein which binds CRM1 and Rev. Moreover, DDX3's necessity for Rev/RRE/CRM1 function was demonstrated by knock-down of cell endogenous DDX3. Finally, because DDX3 locates to nuclear pore complexes (NPC), Yedavalli et al. (12) further proposed that this human helicase, like the analogous yeast Dbp5p (11), may function with Rev/CRM1 to remodel and 'thread' large unspliced HIV-1 RNAs through the nuclear pore, facilitating their final release to the cytoplasmic side of the NPC.