原创力文档role of psip1ledgfp75 in lentiviral infectivity and integration targetingpsip1ledgfp75在慢病毒传染性和集成目标.pdfVIP
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role of psip1ledgfp75 in lentiviral infectivity and integration targetingpsip1ledgfp75在慢病毒传染性和集成目标
Role of PSIP1/LEDGF/p75 in Lentiviral Infectivity and
Integration Targeting
1. 1. 2 4¤ 3 2 3 4
Heather M. Marshall , Keshet Ronen , Charles Berry , Manuel Llano , Heidi Sutherland , Dyana Saenz , Wendy Bickmore , Eric Poeschla ,
Frederic D. Bushman1*
1 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Department of
Family, Preventive Medicine, San Diego School of Medicine, University of California at San Diego, San Diego, California, United States of America,
3 Medical Research Council (MRC) Human Genetics Unit, Edinburgh, United Kingdom, 4 Molecular Medicine Program, Mayo Clinic College of
Medicine, Rochester, Minnesota, United States of America
Background. To replicate, lentiviruses such as HIV must integrate DNA copies of their RNA genomes into host cell
chromosomes. Lentiviral integration is favored in active transcription units, which allows efficient viral gene expression after
integration, but the mechanisms directing integration targeting are incompletely understood. A cellular protein, PSIP1/LEDGF/
p75, binds tightly to the lentiviral-encoded integrase protein (IN), and has been reported to be important for HIV infectivity
and integration targeting. Methodology. Here we report studies of lentiviral integration targeting in 1) human cells with
intensified RNAi knockdowns of PSIP1/LEDGF/p75, and 2) murine cells with homozygous gene trap mutations in the PSIP1/
LEDGF/p75 locus. Infections with vectors derived from equine infections anemia virus (EIAV) and HIV were compared.
Integration acceptor sites were analyzed by DNA bar coding and pyrosequencing. Conclusions/Signifi
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