The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization

By in situ hybridization analysis and immunoprecipitations following transfection of COS cells, we show that the Rev protein of the human immunodeficiency virus is necessary for envelope protein expression, which is correlated with the appearance in the cytoplasm of envelope-specific RNA. In the absence of cotransfection with a plasmid expressing Rev, envelope-specific RNA is retained in the nucleus. Several cis-acting sites in the envelope are involved, one of which is between nucleotides 7330 and 7735 and is required for the response to Rev. Other sequences (nucleotides 5797-7330 and 7735-7989) are involved in the apparent retention of the envelope-specific RNA in the nucleus in the absence of Rev and its response element. Because Rev affects the localization of envelope RNA both in the presence and in the absence of the normal splice sites on the RNA, the mechanism of Rev action is independent of splicing.