Stimulation of the HIV-1 integrase enzymatic activity and cDNA integration by a peptide derived from the integrase protein.
Here we describe the features of a peptide that was selected from the human immunodeficiency virus Type 1 (HIV-1) Integrase (IN) peptide library which interacts with both, the viral Rev and IN proteins. Because of its ability to stimulate the IN enzymatic activity this peptide was designated INS (IN stimulatory). Modification of its amino acid sequence revealed that replacement of its C-terminal lysine by glutamic acid (INS K188E) converts it from a stimulatory peptide to an inhibitory one. Both peptides promoted the dissociation of a previously described complex formed between Rev and IN whose formation results in IN inactivation. INS and INS K188E penetrated HIV-1-infected cells and caused stimulation and inhibition of viral genome integration, respectively. Using cultured cells infected with a DeltaRev HIV revealed that INS can directly activate the viral IN. These results suggest that the stimulatory effect of INS in wild-type virus-infected cells is due to a dual effect: it dissociates the inactive Rev-IN complex and directly activates the free IN.
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Aviad
A
Levin
Zvi
Z
Hayouka
Markus
M
Helfer
Ruth
R
Brack-Werner
Assaf
A
Friedler
Abraham
A
Loyter
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002460:Cell Line; D002463:Cell Membrane Permeability; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019151:Peptide Library; D011485:Protein Binding; D016662:Virus Integration; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D018076:DNA, Complementary; D004279:DNA, Viral; D010446:Peptide Fragments; D019151:Peptide Library; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1