Function of HIV Nef

  • Negative regulatory factor (Nef) is an accessory protein which enhances viral pathogenesis [1].

  • Nef downregulates CD4 receptors and MHC molecules [1].

  • Nef promotes the viral release and the cell-to-cell transmission.

  • Nef activates the apoptosis and involves with the clathrin-dependent endocytic pathways. Nef is incorporated in the viral particles [1].

Reference

  1. Laguette N, Bregnard C, Benichou S, Basmaciogullari S: Human immunodeficiency virus (HIV) type-1, HIV-2 and simian immunodeficiency virus Nef proteins. Molecular aspects of medicine 2010, 31(5):418-433.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Nef

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

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  MGGKWSKSSV IGWPTVRERM RRAEPAADRV GAASRDLEKH GAITSSNTAA 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  TNAACAWLEA QEEEEVGFPV TPQVPLRPMT YKAAVDLSHF LKEKGGLEGL 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  IHSQRRQDIL DLWIYHTQGY FPD*QNYTPG PGVRYPLTFG WCYKLVPVEP 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  DKIEEANKGE NTSLLHPVSL HGMDDPEREV LEWRFDSRLA FHHVARELHP 
  201  206
  |    |
  EYFKNC

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

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  MGGAISMRRS RPSGDLRQRL LRARGETYGR LLGEVEDGYS QSPGGLDKGL 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  SSLSCEGQKY NQGQYMNTPW RNPAEEREKL AYRKQNMDDI DEEDDDLVGV 
  101    110        120        130        140        150
  |        |          |          |          |          | 
  SVRPKVPLRT MSYKLAIDMS HFIKEKGGLE GIYYSARRHR ILDIYLEKEE 
  151    160        170        180        190        200
  |        |          |          |          |          | 
  GIIPDWQDYT SGPGIRYPKT FGWLWKLVPV NVSDEAQEDE EHYLMHPAQT 
  201    210        220        230        240        250
  |        |          |          |          |          | 
  SQWDDPWGEV LAWKFDPTLA YTYEAYVRYP EEFGSKSGLS EEEVRRRLTA 
  251    260
  |        | 
  RGLLNMADKK ETR

(3) Coloring scheme for above amino acids

  1. 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

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

    • N - Asn - Asparagine

    • Q - Gln - Glutamine

    • S - Ser - Serine

    • T - Thr - Threonine

  3. Amino acids with positive charged side chains:

    • H - His - Histidine

    • K - Lys - Lysine

    • R - Arg - Arginine

  4. Amino acids with negative charged side chains:

    • D - Asp - Aspartic acid

    • E - Glu - Glutamic acid

  5. Amino acids with aromatic side chains:

    • F - Phe - Phenylalanine

    • Y - Tyr - Tyrosine

    • W - Trp - Tryptophan

  6. Cysteine: C - Cys - Cysteine

  7. Glycine: G - Gly - Glycine

  8. Proline: P - Pro - Proline

Amino acid variations at HIV-1 Nef

Here, we visualize the prevalence of amino acid variations at the HIV-1 Nef 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 Nef inhibitors, RT inhibitors and Nef inhibitors using HIVdb V6.0 .

Visualization

Our sequence dataset of HIV-1 subtype B Nef 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.

img

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Please cite our article:

  1. 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 Nef

Here, we visualize the secondary structure of HIV-1 Nef using PDBSum (PDB code: 4EMZ)



(2) Tertiary structure of HIV-1 Nef

Here, we provide a structure movie of Nef using PyMOL V1.7 (PDB code: 4EMZ). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Localization

(1) Coding region of Nef at the HIV genome


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

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


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Nef

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



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

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



Protein-protein interactions