TAILIEUCHUNG - Báo cáo y học: " Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells"

Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral cDNA in LEDGF/p75-knockdown cells | Levin et al. Virology Journal 2010 7 177 http content 7 1 177 VIROLOGY JOURNAL RESEARCH Open Access Peptides derived from the HIV-1 integrase promote HIV-1 infection and multi-integration of viral eDNA in LEDGF p75-knockdown cells 1 2 2 1 Aviad Levin Zvi Hayouka Assaf Friedler Abraham Loyter Abstract 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-knokdown 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. Background Productive infection of susceptible cells by Human immunodeficiency virus type 1 HIV-1 has been shown to require in addition to virus-encoded proteins the presence of the host cellular protein .

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