Involvement of human immunodeficiency virus type-1 splice sites in the cytoplasmic accumulation of viral RNA.

To define the role of human immunodeficiency virus type 1 splice sites in the cytoplasmic accumulation of viral RNAs, sequential deletion mutagenesis on an infectious proviral clone of HIV-1 was performed. Deletion of the majority of intron sequences, containing previously identified CRS, did not attenuate CRS activity. Retention of either the first or second tat intron preserved CRS activity. RNAs containing splice donor sequences, in the absence of known downstream splice acceptor sequences, retained CRS activity. Unexpectedly, these splice donors were still utilized for splicing. These results indicate that the major HIV-1 splice donors can function as CRS and function to negatively regulate the cytoplasmic accumulation of HIV-1 RNAs in COS cells.