Abstract:
:Transcriptional co-activator LEDGF/p75 is the major cellular interactor of HIV-1 integrase (IN), critical to efficient viral replication. In this work, a series of INs from the Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Spumavirus and Lentivirus retroviral genera were tested for interaction with the host factor. None of the non-lentiviral INs possessed detectable affinity for LEDGF in either pull-down or yeast two-hybrid assays. In contrast, all lentiviral INs examined, including those from bovine immunodeficiency virus (BIV), maedi-visna virus (MVV) and equine infectious anemia virus (EIAV) readily interacted with LEDGF. Mutation of Asp-366 to Asn in LEDGF ablated the interaction, suggesting a common mechanism of the host factor recognition by the INs. LEDGF potently stimulated strand transfer activity of divergent lentiviral INs in vitro. Unprecedentedly, in the presence of the host factor, EIAV IN almost exclusively catalyzed concerted integration, whereas HIV-1 IN promoted predominantly half-site integration, and BIV IN was equally active in both types of strand transfer. Concerted BIV and EIAV integration resulted in 5 bp duplications of the target DNA sequences. These results confirm that the interaction with LEDGF is conserved within and limited to Lentivirus and strongly argue that the host factor is intimately involved in the catalysis of lentiviral DNA integration.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Cherepanov Pdoi
10.1093/nar/gkl885subject
Has Abstractpub_date
2007-01-01 00:00:00pages
113-24issue
1eissn
0305-1048issn
1362-4962pii
gkl885journal_volume
35pub_type
杂志文章abstract::Mutations in mammalian and Drosophila Hel308 and PolQ paralogues cause genome instability but their helicase functions are mysterious. By in vivo and in vitro analysis, we show that Hel308 from archaea (Hel308a) may act at stalled replication forks. Introducing hel308a into Escherichia coli dnaE strains that condition...
journal_title:Nucleic acids research
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doi:10.1093/nar/gkx017
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更新日期:2001-01-15 00:00:00
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更新日期:2011-04-01 00:00:00
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journal_title:Nucleic acids research
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更新日期:2007-01-01 00:00:00
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pub_type: 指南,杂志文章
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更新日期:2004-02-09 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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