Effect of Ku80 depletion on the preintegrative steps of HIV-1 replication in human cells.

Abstract:

: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.

journal_name

Virology

journal_title

Virology

authors

Jeanson L,Subra F,Vaganay S,Hervy M,Marangoni E,Bourhis J,Mouscadet JF

doi

10.1006/viro.2002.1515

subject

Has Abstract

pub_date

2002-08-15 00:00:00

pages

100-8

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042682202915151

journal_volume

300

pub_type

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