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Retroviral intasome assembly and inhibition of DNA strand transfer
TLDR
The crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA is presented, defining the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs. Expand
Flexible use of nuclear import pathways by HIV-1.
TLDR
A fragment of the cleavage and polyadenylation factor 6, CPSF6, is identified as a potent inhibitor of HIV-1 infection and highlights a single residue in CA as essential in regulating interactions with NUPs. Expand
Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.
TLDR
The crystal structure of the catalytically active core domain of HIV-1 integrase was determined and it is revealed that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. Expand
LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration.
TLDR
Results reveal LEDGF/p75 as a critical targeting factor, commandeering lentiviruses from promoter- and/or CpG island-proximal pathways that are favored by other members of Retroviridae. Expand
Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen
TLDR
A large-scale small interfering RNA screen was performed to identify host factors required by HIV-1 and more than 250 HIV-dependency factors (HDFs) were identified, suggesting that viruses evolve in host cells that optimally perform the functions required for their life cycle. Expand
Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity
TLDR
This work shows that the purified Cas1–Cas2 complex integrates oligonucleotide DNA substrates into acceptor DNA to yield products similar to those generated by retroviral integrases and transposases, and explains the significance of CRISPR repeats in providing sequence and structural specificity for Cas2-mediated adaptive immunity. Expand
Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75.
TLDR
The crystal structure of the dimeric catalytic core domain of HIV-1 IN complexed to the IN-binding domain of LEDGF is reported, showing the backbone conformation of residues 168-171 from one monomer and a hydrophobic patch that is primarily comprised of alpha-helices 1 and 3 of the second IN monomer. Expand
HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer
TLDR
Results suggest that both reactions occur by a one-step mechanism without involvement of a covalent protein-DNA intermediate in HIV-1 integration. Expand
Identification of discrete functional domains of HIV‐1 integrase and their organization within an active multimeric complex.
TLDR
A minimal set of functional integrase domains are identified that are sufficient for 3′ processing and DNA strand transfer and find that some domains are contributed in trans by separate monomers within the functional complex. Expand
Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication
TLDR
This work has introduced site-directed changes into an infectious DNA clone of HIV-1 and show that integrase mutations can affect virus replication at a variety of steps, including mutations that altered virion morphology, levels of particle-associated integrase and reverse transcriptase, and viral DNA synthesis. Expand
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