Identification of a novel splice acceptor in the HIV-1 genome: independent expression of the cytoplasmic tail of the envelope protein.

Multiple splicing sites exist in the RNA genome of the human immunodeficiency virus type 1 (HIV-1). In a screen for subgenomic forms of the HIV-1 genome that could be transferred to fresh cells by virus infection, we identified a novel spliced variant of HIV-1 RNA that uses a hitherto unknown splice acceptor site within the envelope (Env) gene. We demonstrate that this splice acceptor is infrequently used in HIV-infected T cells. Interestingly, an AUG initiator codon is created at this splice junction which has the potential to direct the synthesis of the cytoplasmic tail of the Env gp41 protein. Transient transfection experiments with the new cDNA cloned in an expression vector demonstrated efficient utilization of this start codon and the C-terminus of the Env open reading frame. Independent expression of the 152 amino acid long, intracellular Env domain provides novel regulatory mechanisms for modulating viral infectivity and perhaps pathogenicity.