Chimeric nucleic acids and proteins for inhibiting HIV-1 expression

DETAILED DESCRIPTION OF THE INVENTION A fusion protein according to the invention includes NS1 and Rev proteins or fragments or derivatives of the NS1 and Rev proteins.
The NS1protein, fragment or derivative may be directly joined by a peptide bond to the Rev protein, fragment or derivative.
Alternatively, the NS1 and Rev components may be linked by a peptide linker ranging in length from one amino acid residue through 75 or more residues.
In another alternative, the linker may be an organic polymer.
5.
1 BRIEF DESCRIPTION OF THE FIGURES FIG.
1.
Constructs of various NS1 and Rev hybrids.
HIV-1 Rev wild type (Rev) or several mutant proteins (RevM5 and RevM 10) were attached to the C-terminal end of NS1 (wild type or mutant NS1).
NS1-Rev, fusion protein between wild-type NS1 and wild-type Rev.
NSM2-Rev, fusion protein between NSM2 (RNA-binding domain mutant of NS1 ) and wild-type Rev.
NSM2-RevM10, fusion protein between NSM2 and RevM10(effector domain mutant of Rev).
NS.
DELTA.
2-RevM5, fusion of NS.
DELTA.
2 (NS1 with effector domain deletion) with RevM5 (Rev RNA-binding domain mutant).
NSD2-Rev, fusion of NS.
DELTA.
2 with wild-type Rev.
B1: RNA binding domain of NS1 protein.
B2:Rev RNA binding domain.
E1: NS1 effector domain.
E2:Rev effector domain.
**: amino acid mutation.
FIG.
2.
The effect of wild-type fusion between NS1 and Rev (NS1-Rev) on the transport of tat pre-mRNA.
293 cells were cotransfected with the plasmid encoding the target mRNA (pgtat) and the indicated PBC12 plasmid encoding Rev, NS1-Rev or Rev and NS1-Rev at different ratio (1:1, 2:1 and 3:1).
The amount used for each plasmid was 5 .
mu.
g in each transfection.
tat (s), protected fragment for spliced tat mRNA.
P, undigested S1 probe.
FIG.
3.
A hybrid between an NS1 binding domain mutant and wild-type Rev (NSM2-Rev) can reverse the Rev effect on tat pre-mRNA transport.
293 cells were cotransfected with plasmid encoding for the target mRNA (pgtat) and the indicated PBC12 plasmid encoding Rev (lanes 1 & 2), NSM2-Rev (lanes 3 & 4) or NSM2-Rev and Rev at increasing ratio (lanes 5-12)