HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer

@article{Engelman1991HIV1DI,
  title={HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer},
  author={Alan N. Engelman and Kiyoshi Mizuuchi and Robert Craigie},
  journal={Cell},
  year={1991},
  volume={67},
  pages={1211-1221}
}

Retroviral DNA integration: reaction pathway and critical intermediates

It is shown that HIV‐1 integrase forms stable synaptic complexes in which a tetramer of integrase is stably associated with a pair of viral DNA ends, which define the series of stable nucleoprotein complexes that mediate retroviral DNA integration.

Retroviral DNA Integration

At least two host proteins, HMG-I(Y) and BAF, have been shown to increase the efficiency of the integration reaction, and small duplications of the host DNA, characteristic of the viral IN, are found at the sites of insertion.

Retroviral Integrase Structure and DNA Recombination Mechanism.

X-ray crystal structures of prototype foamy virus integrase-DNA complexes revealed the architectures of the key nucleoprotein complexes that form sequentially during the integration process and explained the roles of active site metal ions in catalysis.

Retroviral DNA Integration

The molecular mechanism of retroviral DNA integration is reviewed, with an emphasis on reaction chemistries and architectures of the nucleoprotein complexes involved, and the latest advances on anti-integrase drug development for the treatment of AIDS are discussed.

Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase

It is demonstrated that the palindrome cleavage occurs via a two-step mechanism leading to a blunt-ended DNA product, followed by a classical 3′-processing reaction; this cleavage leads to integrase-dependent integration, highlighted by a 5-bp duplication of the host genome.

(LTR) DNA circles are a substrate for HIV-1 integrase

It is demonstrated that the palindrome cleavage occurs via a two-step mechanism leading to blunt-ended DNA product, followed by a classical 3’-processing reaction; this cleavage leads to integrase-dependent integration, highlighted by a 5-bp duplication of the host genome.

Processing of Viral DNA Ends Channels the HIV-1 Integration Reaction to Concerted Integration

It is found that blunt-ended DNA is a better substrate for the biologically relevant reaction of concerted integration of pairs of viral DNA ends, and differential effects of mutation of a residue in the C-terminal domain of integrase on concerted versus half-site integration implicate protein-protein interactions involving this domain as important for concerted integration.

Molecular mechanism of retroviral DNA integration.

Human immunodeficiency virus type 1 integration protein: DNA sequence requirements for cleaving and joining reactions

Using purified integration protein (IN) from human immunodeficiency virus (HIV) type 1 and oligonucleotide mimics of viral and target DNA, we have investigated the DNA sequence specificity of the
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References

SHOWING 1-10 OF 40 REFERENCES

A covalent complex between retroviral integrase and nicked substrate DNA.

Computer-assisted alignment of 80 retroviral and retrotransposon IN sequences identified one serine that is conserved in all of these proteins and three less-conserved threonine residues, which provide support for the participation of a covalent IN-DNA intermediate in retroViral integration.

Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein.

The structure of the initial covalent product of an in vitro retroviral integration reaction is analyzed and the structures of the ends of the unintegrated linear viral DNA molecules present in vivo in cells infected with murine leukemia virus (MLV).

Activities of human immunodeficiency virus (HIV) integration protein in vitro: specific cleavage and integration of HIV DNA.

  • F. BushmanR. Craigie
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1991
A simple in vitro system that carries out the integration reaction and the use of this system to probe the mechanism of integration provides a simple screen for testing candidate inhibitors of HIV IN protein; some such inhibitors might have useful antiviral activity.

The avian retroviral integration protein cleaves the terminal sequences of linear viral DNA at the in vivo sites of integration

These results provide the first enzymatic support using purified retroviral proteins for a linear DNA precursor to the integrated provirus and define the sequence requirements for site-selective nicking; nucleotides near the cleavage site are most critical for activity.

Circular DNA of human immunodeficiency virus: analysis of circle junction nucleotide sequences

Comparison of the termini of linear viral DNA with sequences at the junctions between the integrated provirus and the host chromosome has revealed that for most retroviruses 2 bp are removed from each end of the linear HIV-1 viral DNA during integration.

A nucleoprotein complex mediates the integration of retroviral DNA.

Analysis of the native state of viral DNA in cells acutely infected by murine leukemia virus shows that the viral capsid protein is part of the active nucleoprotein complex, but recognition of the complex by only a subset of anti-capsid sera implies that the protein is constrained conformationally.