Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells.
BACKGROUND
The presence of the cellular Lens Epithelium Derived Growth Factor p75 (LEDGF/p75) protein is essential for integration of the Human immunodeficiency virus type 1 (HIV-1) cDNA and for efficient virus production. In the absence of LEDGF/p75 very little integration and virus production can be detected, as was demonstrated using LEDGF/p75-knockdown cells.


RESULTS
Here we show that the failure to infect LEDGF/p75-knockdown cells has another reason aside from the lack of LEDGF/p75. It is also due to inhibition of the viral integrase (IN) enzymatic activity by an early expressed viral Rev protein. The formation of an inhibitory Rev-IN complex in virus-infected cells can be disrupted by the addition of three IN-derived, cell-permeable peptides, designated INr (IN derived-Rev interacting peptides) and INS (IN derived-integrase stimulatory peptide). The results of the present work confirm previous results showing that HIV-1 fails to infect LEDGF/p75-knockdown cells. However, in the presence of INrs and INS peptides, relatively high levels of viral cDNA integration as well as productive virus infection were obtained following infection by a wild type (WT) HIV-1 of LEDGF/p75-knockdown cells.


CONCLUSIONS
It appears that the lack of integration observed in HIV-1 infected LEDGF/p75-knockdown cells is due mainly to the inhibitory effect of Rev following the formation of a Rev-IN complex. Disruption of this inhibitory complex leads to productive infection in those cells.
Levin
Aviad
A
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences; The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Hayouka
Zvi
Z
Friedler
Assaf
A
Loyter
Abraham
A
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D055785:Gene Knockdown Techniques; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D016662:Virus Integration; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D004279:DNA, Viral; C504649:PSIP1 protein, human; D014157:Transcription Factors; 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