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We constructed 16 deletion mutants from an infectious molecular clone of feline immunodeficiency virus (FIV) and a reporter plasmid carrying the bacterial chloramphenicol acetyltransferase (CAT) gene to identify the rev transactivator activity of the virus. Cotransfections of various mutants and the rev reporter clone bearing a portion of FIV env in addition to the CAT gene revealed that the sequence important for the augmentation of CAT production was located in three separate parts of the virus genome. This enhancement was FIV specific in that the human retrovirus rev and rex gene products did not activate the reporter. The phenotypic properties of an FIV proviral mutant containing a small deletion in the genome were similar to those of rev mutants derived from primate immunodeficiency viruses. These results indicate that FIV, like the other lentiviruses, contains the rev gene in its genome.

The Rex proteins of human T-cell leukemia virus types I and II (HTLV-I and HTLV-II) induce cytoplasmic expression of unspliced gag-pol mRNA and singly spliced env mRNA and are critical for virus replication. Two rex gene products, p27rex and p21rex of HTLV-I and p26rex and p24rex of HTLV-II, have been detected in HTLV-infected cells; however, the structural and biological relationship of the proteins has not been clearly elucidated. Endoproteinase digestion and phosphoamino acid analysis of HTLV-II Rex indicated that p24rex has the same amino acid backbone as p26rex and that the larger apparent molecular size of p26rex is attributable to serine phosphorylation.

Lentiviruses encode proteins that regulate viral gene expression. One class of regulatory proteins are the HIV-1 REV and HTLV-1 REX proteins which are essential gene products for virus replication (Feinberg et al., 1986; Sodroski et al., 1986; Seiki et al., 1988). Mutations within these genes ablate the expression of viral structural proteins without affecting the total level of viral RNA in the nucleus (Felber et al., 1989; Terwilliger et al., 1988; Knight et al., 1987; Emerman et al., 1989; Hammarskjold et al., 1989; Nosaka et al., 1989). Transient expression and virus rescue experiments have led to the identification of a cis-acting sequence in the transcribed RNA of HIV-1 and HTLV-1 termed the REV or REX responsive element (RRE and RxRE respectively) that is essential for REV or REX function (Inoue et al., 1987; Seiki, et al., 1988; Malim et al., 1989; Hadzopoulou-Cladaras et al., 1989). Genetic studies of these genes and their cis-acting elements have led to the following hypothesis: the REV and REX gene products complete viral gene expression and replication by facilitating the transport from the nucleus of RNA transcripts encoding structural proteins and new viral genomes. One proposed step in this process involves the direct interaction of REV and REX with viral RNA transcripts in the nucleus.