The Lentivirus Regulatory Proteins REV and REX are Site Specific RNA Binding Proteins

Abstract

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; Hammarskjöld 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.