Composition and method for activating latent human immunodeficiency virus (hiv)

Abstract

Provided are compositions and methods for activating latent Human Immunodeciency Virus (HIV). The compositions and methods may utilize a recombinant peptide that has a DNA-binding zinc finger domain specific to the HIV LTR sequence. The recombinant peptide may also have a transcription factor (e.g. a transcription activator) that is conjuated to the zinc finger domain. Also provided are methods of treating HIV in a subject in need of the treatment. The method may involve activation of latent HIV in cells of the subject and selectively removing such cells from the subject, providing complete and effective treatment of HIV.

1 - 32 . (canceled) 
     
     
         33 . A recombinant peptide comprising a zinc finger domain, wherein said recombinant peptide binds to a target nucleotide sequence, wherein said target nucleotide sequence is a long terminal repeat (LTR) sequence of Human Immunodeficiency Virus (HIV), and wherein said recombinant peptide comprises SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25. 
     
     
         34 . The recombinant peptide of  claim 33 , wherein said recombinant peptide comprises SEQ ID NO: 12 or a derivative thereof having at least 75% nucleotide sequence identity to SEQ ID NO. 12. 
     
     
         35 . The recombinant peptide of  claim 33 , wherein the recombinant peptide further comprises a transcriptional activator. 
     
     
         36 . The recombinant peptide of  claim 35 , wherein the transcriptional activator comprises one or more of viral protein P(VPR), p65 transactivating subunit of NF-kappa B, heat-shock factor 1 (HSF) activation domain, VP64 (tetramer of VP16) activation domain, synergistic activation mediator (SAM), or any derivatives thereof. 
     
     
         37 . The recombinant peptide of  claim 36 , wherein the transcriptional activator comprises a VPR peptide, and wherein the VPR peptide comprises SEQ ID NO: 13, or a derivative thereof having at least 50% amino acid sequence identity to SEQ ID NO. 13. 
     
     
         38 . The recombinant peptide of  claim 37 , wherein the VPR peptide is encoded by SEQ ID NO: 4, or a derivative thereof having at least 50% nucleotide sequence identity to SEQ ID NO. 4. 
     
     
         39 . The recombinant peptide of  claim 37 , wherein the recombinant peptide further comprises one or more of (a) one or more nuclear localization signal (NLS) sequences, (b) a peptide comprising a TAT peptide, (c) a myc-tag sequence, and (d) a peptide comprising a cleavable maltose binding domain. 
     
     
         40 . The recombinant peptide of  claim 39 , wherein the one or more NLS sequences comprise SEQ ID NO: 15, or a derivative thereof having at least 90% amino acid sequence identity to SEQ ID NO. 15. 
     
     
         41 . The recombinant peptide of  claim 39 , wherein the TAT peptide comprises SEQ ID NO: 14, or a derivative thereof having at least 90% amino acid sequence identity to SEQ ID NO. 14. 
     
     
         42 . The recombinant peptide of  claim 39 , wherein said myc-tag sequence comprises SEQ ID NO: 16, or a derivative thereof having at least 90% amino acid sequence identity to SEQ ID NO. 16. 
     
     
         43 . The recombinant peptide of  claim 39 , wherein the recombinant peptide comprises SEQ ID NO: 18, or a derivative thereof having at least 90% amino acid sequence identity to SEQ ID NO. 18. 
     
     
         44 . The recombinant peptide of  claim 39 , wherein the recombinant peptide is encoded by SEQ ID NO: 9, or a derivative thereof having at least 90% nucleotide sequence identity to SEQ ID NO. 9. 
     
     
         45 . An expression vector comprising SEQ ID NO: 9, wherein SEQ ID NO: 9 is expressed under the control of a CMV promoter, a HI promoter or an EF1 alpha promoter. 
     
     
         46 . The recombinant peptide of  claim 33 , wherein the recombinant peptide can cross a blood brain barrier in a subject upon administration to said subject. 
     
     
         47 . The recombinant peptide of  claim 33 , wherein said target nucleotide sequence comprises SEQ ID NO. 1 or a derivative thereof having at least 90% nucleotide sequence identity to SEQ ID NO. 1. 
     
     
         48 . The recombinant peptide of  claim 33 , wherein said target nucleotide sequence comprises SEQ ID NO. 2 or a derivative thereof having at least 90% nucleotide sequence identity to SEQ ID NO. 2. 
     
     
         49 . A method of activating a latent HIV in a cell, the method comprising: administering the recombinant peptide of  claim 33  to the cell. 
     
     
         50 . The method of  claim 49 , wherein the cell was previously infected with HIV and the HIV or progeny thereof is in a latent stage. 
     
     
         51 . The method of  claim 50 , wherein the cell is T cell, macrophage, monocyte or microglial cell. 
     
     
         52 . A method of treating latent stage Human Immunodeficiency Virus (HIV) in a subject in need thereof, the method comprising administering the recombinant peptide of  claim 33  to the subject. 
     
     
         53 . A method of activating a latent HIV in a cell, the method comprising: administering the expression vector of  claim 45  to the cell. 
     
     
         54 . A method of treating latent stage Human Immunodeficiency Virus (HIV) in a subject in need thereof, the method comprising administering the expression vector of  claim 45  to the subject.