IDENTIFICATION OF THE ACTIVATION DOMAIN OF EQUINE INFECTIOUS-ANEMIA VIRUS REV

Several members of the lentivirus family of complex retroviruses have been shown to encode proteins that are functionally equivalent to the Rev posttranscriptional regulatory protein of human immunodeficiency v irus type 1 (HIV-1). Furthermore, the domain organization of HIV-1 Rev , featuring a highly basic N-terminal RNA binding domain and a leucine -rich C-terminal effector domain, has also been shown to be highly con served among Rev proteins derived from not only the primate but also t he ovine and caprine lentiviruses. Although it has therefore appeared highly probable that the lentivirus equine infectious anemia virus (EI AV) also encodes a Rev, the predicted amino acid sequence of this puta tive EIAV regulatory protein does not display any evident homology to the basic and leucine-rich motifs characteristic of other known Rev pr oteins. By fusion of different segments of the proposed EIAV Rev prote in to the well-defined RNA binding domain of either HIV-1 or visna vir us Rev, we have identified a segment of this EIAV protein that can eff iciently substitute in cis for the otherwise essential activation moti f. Interestingly, the minimal EIAV Rev activation motif identified in this study comprises approximately 18 amino acids located toward the p rotein N terminus that lack any evident similarity to the leucine-rich activation domains found in these other lentivirus Rev proteins. It t herefore appears that the Rev protein of EIAV, while analogous in func tion to Rev proteins defined in lentiviruses of primate, ovine, and ca prine origin, is nevertheless distinguished by an entirely novel domai n organization.