Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses

Wu, Xiaolin; Li, Yuan; Crise, Bruce; Burgess, Shawn M.; Munroe, David J.

doi:10.1128/jvi.79.8.5211-5214.2005

Cited by 144 publications

(185 citation statements)

References 24 publications

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“…The overall consensus sequences at these positions are RWRR and YKRY (using standard International Union of Biochemistry codes). While FIV nucleotide preferences shared a symmetry pattern similar to those reported for HIV, SIV, ASLV, and MLV (9,27), the FIV preferences differed in primary sequence from HIV, MLV, SIV, and ASLV (9,27). These results suggest that each retrovirus may have distinct, but not absolute, base preferences at integration sites.…”

mentioning

confidence: 46%

Integration Site Choice of a Feline Immunodeficiency Virus Vector

Kang

Moressi²,

Scheetz³

et al. 2006

J Virol

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mentioning

confidence: 46%

Integration Site Choice of a Feline Immunodeficiency Virus Vector

Kang

Moressi²,

Scheetz³

et al. 2006

J Virol

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“…Although harder to address experimentally, it has not been ruled out that the ensemble of host cell enzymes that carries out gap repair is not properly entrained in the absence of p75 and the semi-joined provirus is "repaired" by its removal; however, the increases in 2-LTR circles that have been seen in p75-deficient cells weigh against this. Note also that p75 knockout did not affect the wellestablished tendency of retroviral integrations to occur at weakly conserved yet virus and/or genus-specific DNA sequences with palindrome-approximating symmetry [48,61,116,136,162,163], indicating cofactor-independent, presumably IN-autonomous selectivity that depends on the local DNA sequence irrespective of larger scale genomic features or the G/C content of the DNA [101].…”

Section: Modeling P75 Function In the Hiv Life Cyclementioning

confidence: 89%

Integrase, LEDGF/p75 and HIV replication

Poeschla

2008

Cell. Mol. Life Sci.

115

104

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HIV integrates a DNA copy of its genome into a host cell chromosome in each replication cycle. The essential DNA cleaving and joining chemistry of integration is known, but there is less understanding of the process as it occurs in a cell, where two complex and dynamic macromolecular entities are joined: the viral pre-integration complex and chromatin. Among implicated cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking factor or receptor for lentiviral pre-integration complexes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells and/or over-expressing its integrase-binding domain blocks viral replication. Current goals are to establish the underlying mechanisms and to determine whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene therapy.

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“…The palindrome preferences of the various retroviruses seem to reflect preferences of their respective INs (6,28,29). The palindrome preference of HIV-1 does not change in cells that lack LEDGF (8,19).…”

Section: Cbd-ibd Fusions Can Functionally Replace Ledgf To Support Efmentioning

confidence: 99%

“…Genomic DNA was isolated from transduced MEF-KO cells using a QIAamp DNA Blood Mini Kit (Qiagen) or by extracting HIRT pellets (34). Linker-mediated PCR (LM-PCR) was used to amplify the junctions of integration sites and genomic DNA, as described previously (4,29). Genomic DNA samples (2 μg) were digested with restriction enzymes (i) MseI, (ii) Tsp509I, or (iii) a combination of AvrII/NheI/SpeI and then ligated to linkers.…”

Section: Methodsmentioning

confidence: 99%

Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration

Ferris

Hughes

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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127

130

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Lens epithelium-derived growth factor (LEDGF) fusion proteins can direct HIV-1 DNA integration to novel sites in the host genome. The C terminus of LEDGF contains an integrase binding domain (IBD), and the N terminus binds chromatin. LEDGF normally directs integrations to the bodies of expressed genes. Replacing the N terminus of LEDGF with chromatin binding domains (CBDs) from other proteins changes the specificity of HIV-1 DNA integration. We chose two well-characterized CBDs: the plant homeodomain (PHD) finger from ING2 and the chromodomain from heterochromatin binding protein 1α (HP1α). The ING2 PHD finger binds H3K4me3, a histone mark that is associated with the transcriptional start sites of expressed genes. The HP1α chromodomain binds H3K9me2,3, histone marks that are widely distributed throughout the genome. A fusion protein in which the ING2 PHD finger was linked to the LEDGF IBD directed integrations near the start sites of expressed genes. A similar fusion protein in which the HP1α chromodomain was linked to the LEDGF IBD directed integrations to sites that differed from both the PHD finger fusion-directed and LEDGF-directed integration sites. The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy.chromatin | histone marks | lentiviral vectors R etroviruses can integrate their DNAs at many sites in host DNA (1), but different retroviruses have different integration site preferences (2-9). HIV-1 and simian immunodeficiency virus DNAs preferentially integrate into expressed genes, murine leukemia virus (MLV) DNA preferentially integrates near transcriptional start sites (TSSs), and avian sarcoma leukosis virus (ASLV) and human T cell leukemia virus (HTLV) DNAs integrate nearly randomly, showing a slight preference for genes. This suggests that the preintegration complexes (PICs) of the different retroviruses interact with different factors in host cell chromatin and that the integration site preferences are determined by the distribution of the different host cell factors. Studies of the specificity of integration of yeast retrotransposons, which are distantly related to retroviruses, provide strong support for this interpretation (10-12). The host factors that MLV, ASLV, and HLTV PICs interact with are not known.

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Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses

Cited by 144 publications

References 24 publications

Integration Site Choice of a Feline Immunodeficiency Virus Vector

Integration Site Choice of a Feline Immunodeficiency Virus Vector

Integrase, LEDGF/p75 and HIV replication

Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration

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