Human immunodeficiency virus type 1 Rev-dependent effects on the late gene expression of recombinant human adenovirus

Both human adenovirus type 5 (Ad5) and human immunodeficiency virus (HIV-1) encode functions (E1b 55K/E4 orf6 and Rev respectively) which are needed for the efficient cytoplasmic accumulation of late viral mRNAs and which act post-transcriptionally. The similarity between these two regulatory systems was explored by constructing recombinant Ad5 carrying either one or both of the two components of the HIV-1 system (Rev and its RNA target sequence, RRE) and analysing the effects on Ad5 gene expression. In the presence of a functional Ad5 regulatory system, the HIV-1 system had no detectable effect on Ad5 gene expression. When the Ad5 system was rendered inoperative by mutation, the HIV-1 Rev/RRE system brought about a modest increase in the cytoplasmic accumulation of RRE-containing mRNAs. This was not sufficient to complement effectively the defect due to the Ad5 mutation. These data suggest that HIV-1 Rev acts on a similar pool of nuclear RNA to that targeted by Ad5 E1b 55K/E4 orf6 but functions inefficiently in the situation studied here. Effects were also observed on the accumulation of certain Ad5 mRNAs from which the RRE had been removed by splicing. No change was observed in the balance of production of differentially spliced mRNAs from the RRE-containing primary transcript when Rev was present. These observations are therefore more consistent with a mode of action for Rev that involves commitment of nuclear RNAs to transport than with models in which Rev acts as an inhibitor of splicing.