Article: article from journal or magazin.
Effect of Ku80 depletion on the preintegrative steps of HIV-1 replication in human cells.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
To gain new insights regarding the role of Ku, the DNA-PK DNA-binding component, during lentiviral DNA integration, we have investigated the HIV-1 replication in Ku80-depleted human cells. CEM4fx cells underexpressing the Ku80 factor were selected after transduction by a retroviral vector expressing the Ku80 full-length antisense sequence. De novo infection experiment with NL4.3 HIV-1 strain led to the observation that the viral replication was delayed in the Ku80-depleted cells. Early events of the replicative cycle, including nuclear import of the viral DNA, were not affected. In contrast, the formation of the 2-LTR circles was impaired, thus demonstrating the implication of Ku in HIV-1 DNA circularization, for the first time in human cells. Furthermore, the detection of integrated proviruses by an Alu-LTR-nested PCR amplification method was affected in cells underexpressing Ku80. These results suggest that this factor may also be involved in the mechanisms leading to the stable establishment of HIV-1 provirus.
Antigens, Nuclear, Cell Line, Cell Nucleus/metabolism, DNA Helicases, DNA Repair, DNA Replication, DNA-Binding Proteins/deficiency, DNA-Binding Proteins/metabolism, HIV-1/genetics, Humans, Kinetics, Nuclear Proteins/deficiency, Nuclear Proteins/metabolism, Protein Transport, Transcription Factors/deficiency, Transcription Factors/metabolism, Virus Integration/physiology, Virus Replication/physiology
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