Background Human immunodeficiency virus type-1 (HIV-1) infection is one of the leading causes of death worldwide. Current anti-HIV-1 therapy, referred as highly active antiretroviral therapy (HAART), is based on the use of combination of drugs directed against viral enzymes mainly reverse transcriptase and protease and more recently integrase. Indeed, HAART has dramatically improved the clinical course of the disease. However, the emergence of multi-drug resistant virus strains during treatment highlights the urgent need to develop novel antiretroviral drugs against new HIV-1 targets. HIV-1 is able to hijack cellular machinery for its replication through protein-protein interactions between viral and host cell factors and a rising strategy against HIV-1 infection is to inhibit key virus-cell interactions. Integrase that catalyses HIV-1 viral DNA integration into the host cell genome is currently a focus for the development of new drugs. Several cellular partners of integrase have been identified using different methods. Based on a different strategy, our study aimed to identify new integrase cellular partners.
Methods We used a biotinylated oligonucleotide derived from the viral U3 LTR end as bait to isolate integrase in a streptavidin beads magnetic separation. Proteins co-purified with integrase were analysed by mass spectrometry.
Results Interestingly, our method allowed the identification of new cellular proteins notably p72 and p68 RNA helicases and histone deacetylase 1 (HDAC1) as integrase partners in addition to proteins already reported in literature. The interaction of p72, p68 and HDAC1 proteins with integrase was confirmed by co-immunoprecipitation. In addition, specific knockdown of p72 and p68 RNA helicases and HDAC1 were shown to affect HIV-1 replication.
Conclusions Our data suggest that cellular proteins, p72 and p68 RNA helicases and HDAC1 facilitate HIV-1 replication through interaction with integrase.
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