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Function of HIV Integrase

Integrase is the third enzyme encoded by the pol gene.
After the nuclear import of pre-integration complex (PIC), viral Integrase catalyzes two major reactions (3’-processing and strand transfer reactions) to insert the linear, double-stranded viral DNA into human chromosomes.
In the mature viral particles, Integrase is cleaved from the GagPol polyprotein by viral Protease. Moreover, reverse transcriptase binds with integrase to prevent the catalytic activity of Integrase before viral integration [1].
As part of reverse transcriptase complex, Integrase also plays a role during reverse transcription [2].

Reference

Zhu K, Dobard C, Chow SA: Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J Virol 2004, 78:5045-5055.(Download Article)
Xue B, Mizianty MJ, Kurgan L, Uversky VN: Protein intrinsic disorder as a flexible armor and a weapon of HIV-1. Cell Mol Life Sci 2012, 69:1211-1259.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Integrase

Strain: HIV-1 subtype B HXB2 (ID: K03455)
Fasta format: Download
Reference sequence:

  1       10         20         30         40         50
  |        |          |          |          |          | 
  FLDGIDKAQD EHEKYHSNWR AMASDFNLPP VVAKEIVASC DKCQLKGEAM 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  HGQVDCSPGI WQLDCTHLEG KVILVAVHVA SGYIEAEVIP AETGQETAYF 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  LLKLAGRWPV KTIHTDNGSN FTGATVRAAC WWAGIKQEFG IPYNPQSQGV 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  VESMNKELKK IIGQVRDQAE HLKTAVQMAV FIHNFKRKGG IGGYSAGERI 
  201    210        220        230        240        250
  |        |          |          |          |          | 
  VDIIATDIQT KELQKQITKI QNFRVYYRDS RNPLWKGPAK LLWKGEGAVV 
  251    260        270        280      288
  |        |          |          |        | 
  IQDNSDIKVV PRRKAKIIRD YGKQMAGDDC VASRQDED

(2) Reference sequence for HIV-2 and SIV Integrase

Strain: SIV Mac239 (ID: M33262)
Fasta format: Download
Reference sequence:

  1       10         20         30         40         50
  |        |          |          |          |          | 
  FLEKIEPAQE EHDKYHSNVK ELVFKFGLPR IVARQIVDTC DKCHQKGEAI 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  HGQANSDLGT WQMDCTHLEG KIIIVAVHVA SGFIEAEVIP QETGRQTALF 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  LLKLAGRWPI THLHTDNGAN FASQEVKMVA WWAGIEHTFG VPYNPQSQGV 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  VEAMNHHLKN QIDRIREQAN SVETIVLMAV HCMNFKRRGG IGDMTPAERL 
  201    210        220        230        240        250
  |        |          |          |          |          | 
  INMITTEQEI QFQQSKNSKF KNFRVYYREG RDQLWKGPGE LLWKGEGAVI 
  251    260        270        280        290
  |        |          |          |          | 
  LKVGTDIKVV PRRKAKIIKD YGGGKEVDSS SHMEDTGEAR EVA

(3) Coloring scheme for above amino acids

Amino acids with hydrophobic side chains (normally buried inside the protein core):
- A - Ala - Alanine
- I - Ile - Isoleucine
- L - Leu - Leucine
- M - Met - Methionine
- V - Val - Valine
Amino acids with polar uncharged side chains (may participate in hydrogen bonds):
- N - Asn - Asparagine
- Q - Gln - Glutamine
- S - Ser - Serine
- T - Thr - Threonine
Amino acids with positive charged side chains:
- H - His - Histidine
- K - Lys - Lysine
- R - Arg - Arginine
Amino acids with negative charged side chains:
- D - Asp - Aspartic acid
- E - Glu - Glutamic acid
Amino acids with aromatic side chains:
- F - Phe - Phenylalanine
- Y - Tyr - Tyrosine
- W - Trp - Tryptophan
Cysteine: C - Cys - Cysteine
Glycine: G - Gly - Glycine
Proline: P - Pro - Proline

Amino acid variations at HIV-1 Integrase

Here, we visualize the prevalence of amino acid variations at the HIV-1 Integrase from HIV-1 subtype B.

Protocal of our sequence collection

For HIV-1 subtype B, one sequence per patient was extracted from HIV Los Alamos database (www.hiv.lanl.gov/).
We removed misclassified sequences or sequences with hypermutations, stop codons, ambiguous nucleotides, which were described in our article [1].
We removed sequences conferred partial or full resistance to any of the Integrase inhibitors, RT inhibitors and integrase inhibitors using HIVdb V6.0 .

Visualization

Our sequence dataset of HIV-1 subtype B Integrase included 4725 sequences. In the following picture, HXB2 indices of individual proteins are shown on top of the colored bars. A consensus amino acid at each position is shown beneath the colored bar. Natural variations are shown below the consensus amino acids; proportions (%) are colored red if they were more than 5%; blue otherwise.

HIV-1 protein interaction patterns.

www.virusface.com

Please cite our article:

Guangdi Li, Supinya Piampongsant, Nuno Rodrigues Faria, Arnout Voet, Andrea-Clemencia Pineda-Peña, Ricardo Khouri, Philippe Lemey, Anne-Mieke Vandamme, Kristof Theys. An integrated map of HIV genome-wide variation from a population perspective. Retrovirology 12, 18, doi:10.1186/s12977-015-0148-6 (2015). [PDF] [PubMed Link]

Structure

(1) Secondary structure of HIV-1 Integrase

Here, we visualize the secondary structure of HIV-1 Integrase using PDBSum (PDB code: 1A30)

(2) Tertiary structure of HIV-1 Integrase

Here, we provide a structure movie of Integrase using PyMOL V1.7 (PDB code: 1A30). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Function of HIV Integrase

Integrase is the third enzyme encoded by the pol gene.

After the nuclear import of pre-integration complex (PIC), viral Integrase catalyzes two major reactions (3’-processing and strand transfer reactions) to insert the linear, double-stranded viral DNA into human chromosomes.

In the mature viral particles, Integrase is cleaved from the GagPol polyprotein by viral Protease. Moreover, reverse transcriptase binds with integrase to prevent the catalytic activity of Integrase before viral integration [1].

As part of reverse transcriptase complex, Integrase also plays a role during reverse transcription [2].

Reference

Zhu K, Dobard C, Chow SA: Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J Virol 2004, 78:5045-5055.(Download Article)

Xue B, Mizianty MJ, Kurgan L, Uversky VN: Protein intrinsic disorder as a flexible armor and a weapon of HIV-1. Cell Mol Life Sci 2012, 69:1211-1259.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Integrase

Strain: HIV-1 subtype B HXB2 (ID: K03455)

Fasta format: Download

Reference sequence:

(2) Reference sequence for HIV-2 and SIV Integrase

Strain: SIV Mac239 (ID: M33262)

Fasta format: Download

Reference sequence:

(3) Coloring scheme for above amino acids

Amino acids with hydrophobic side chains (normally buried inside the protein core):

A - Ala - Alanine

I - Ile - Isoleucine

L - Leu - Leucine

M - Met - Methionine

V - Val - Valine

Amino acids with polar uncharged side chains (may participate in hydrogen bonds):

N - Asn - Asparagine

Q - Gln - Glutamine

S - Ser - Serine

T - Thr - Threonine

Amino acids with positive charged side chains:

H - His - Histidine

K - Lys - Lysine

R - Arg - Arginine

Amino acids with negative charged side chains:

D - Asp - Aspartic acid

E - Glu - Glutamic acid

Amino acids with aromatic side chains:

F - Phe - Phenylalanine

Y - Tyr - Tyrosine

W - Trp - Tryptophan

Cysteine: C - Cys - Cysteine

Glycine: G - Gly - Glycine

Proline: P - Pro - Proline

Amino acid variations at HIV-1 Integrase

Here, we visualize the prevalence of amino acid variations at the HIV-1 Integrase from HIV-1 subtype B.

Protocal of our sequence collection

For HIV-1 subtype B, one sequence per patient was extracted from HIV Los Alamos database (www.hiv.lanl.gov/).

We removed misclassified sequences or sequences with hypermutations, stop codons, ambiguous nucleotides, which were described in our article [1].

We removed sequences conferred partial or full resistance to any of the Integrase inhibitors, RT inhibitors and integrase inhibitors using HIVdb V6.0 .

Visualization

HIV-1 protein interaction patterns.

www.virusface.com

Please cite our article:

Structure

(1) Secondary structure of HIV-1 Integrase

Here, we visualize the secondary structure of HIV-1 Integrase using PDBSum (PDB code: 1A30)

(2) Tertiary structure of HIV-1 Integrase

Here, we provide a structure movie of Integrase using PyMOL V1.7 (PDB code: 1A30). Alpha-helix and beta-strand secondary structures are demonstrated by red . I'm sorry; your browser doesn't support HTML5 video in WebM with VP8 or MP4 with H.264.

Localization

(1) Coding region of Integrase at the HIV genome

(2) Localization of Integrase during the HIV-1 life cycle

Here, we visualize the localization of Integrase during the viral life cycle. Red stars indicate the appearance of HIV-1 Integrase.

Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Integrase

Here, we visualize the drug binding pocket of HIV-1 Integrase

(2) List of known inhibitors targeting HIV-1 Integrase

Here, we summarize the published anti-HIV inhibitors which bind to HIV-1 Integrase.

Protein-protein interactions

Here, we provide a structure movie of Integrase using PyMOL V1.7 (PDB code: 1A30). Alpha-helix and beta-strand secondary structures are demonstrated by red .