Specific eradication of HIV-1 from infected cultured cells

No cure or vaccine are currently available for the human immunodeficiency virus type 1 (HIV-1) infection as well as for the resulting Acquired Immunodeficiency syndrome (AIDS) [1]. However, an highly active antiretroviral therapy (HAART), which blocks the activities of the viral reverse transcriptase and protease and inhibits the virus-host fusion process, is presently used [2,3]. The HAART transforms the infection process into a chronic disease [4-6]. Furthermore, the risk of infection can significantly be reduced if the HAART treatment is given right after exposure to the virus [7].New therapeutic approaches and new anti-viral inhibitors are being continuously developed to obtain a better restriction of the HIV-1 infection process [8-19]. However, once the viral cDNA is integrated into the host chromosome it is almost impossible to terminate infection process and cure AIDS. A way to eradicate the integrated viral cDNA from virus infected cells by stimulating the viral Integrase (IN) mediated disintegration process was suggested recently [20,21]. However, this approach is only in its initial steps [20].HIV-1 infected cells, unlike cells infected by other retroviruses, bear only 1-2 copies of integrated viral cDNA/cell [22,23]. This is in spite of the presence of numerous copies of unintegrated viral cDNA [22,24]. Recently we have shown that this restriction is due to inhibition of the viral IN activity as well as of its nuclear import by an early expressed viral Rev protein following Rev-IN interaction [25-30]. Disruption of the Rev-IN complex by IN-derived cell permeable peptides, such as the INS [31] and INrs [28], results in multi-integration of the viral cDNA [26,28,31]. Previous findings have shown that multi-integration of viral DNA in AIDS patients may lead to host genome instability [32]. Indeed, a correlation between promotion of multi-integration and increase in cell death was demonstrated recently by us [25].Based on these observations we have developed