Concerted action of multiple cis-acting sequences is required for Rev dependence of late human immunodeficiency virus type 1 gene expression

Based on the human immunodeficiency virus type 1 (HIV-1) gag gene, subgenom ic reporter constructs have been established allowing the contributions of different cis-acting elements to the Rev dependency of late HIV-1 gene prod ucts to be determined. Modification of intragenic regulatory elements achie ved by adapting the codon usage of the complete gene to highly expressed ma mmalian genes resulted in constitutive nuclear export allowing high levels of Gag expression independent from the Rev/Rev-responsive element system an d irrespective of the absence or presence of the isolated major splice dono r. Leptomycin B inhibitor studies revealed that the RNAs derived from the c odon-optimized gag gene lacking AU-rich inhibitory elements are directed to a distinct, CRM1-independent, nuclear export pathway.