Function of HIV Vpx

  • Vpx is an accessory protein in HIV-2 but absent in HIV-2.

  • Vpx induces the ubiquitin-proteasome-dependent degradation of SAMHD1 [1-3], which restricts the HIV-2 replication in myeloid cells.

  • Vpx is required for HIV-2 reverse transcription [4]

  • Vpx assists the nuclear import of viral pre-integration complex (PIC) [1-3]. A major difference between Vpr in HIV-2 and Vpx in HIV-2 is that Vpr arrests the host cell cycle in the G2 phase, while Vpx targets the host restriction factor SAMHD1 for the proteasomal degradation [1].

Reference

  1. Zhu C, Gao W, Zhao K, Qin X, Zhang Y, Peng X, Zhang L, Dong Y, Zhang W, Li P et al: Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside triphosphate triphosphohydrolase. Nature communications 2013, 4:2722.(Download Article)

  2. Fujita M, Otsuka M, Nomaguchi M, Adachi A: Multifaceted activity of HIV Vpr/Vpx proteins: the current view of their virological functions. Reviews in medical virology 2010, 20(2):68-76.(Download Article)

  3. Ayinde D, Maudet C, Transy C, Margottin-Goguet F: Limelight on two HIV/SIV accessory proteins in macrophage infection: is Vpx overshadowing Vpr? Retrovirology 2010, 7:35.(Download Article)

  4. Fujita M, Otsuka M, Miyoshi M, Khamsri B, Nomaguchi M, Adachi A: Vpx is critical for reverse transcription of the human immunodeficiency virus type 2 genome in macrophages. Journal of virology 2008, 82(15):7752-7756.(Download Article)

Sequence

(1) Reference sequence for HIV-2 and SIV Vpx

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  MEERPPENEG PQREPWDEWV VEVLEELKEE ALKHFDPRLL TALGNHIYNR 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  HGDTLEGAGE LIRILQRALF MHFRGGCIHS RIGQPGGGNP LSAIPPSRSM 
  101
  |
  L

(2) 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

Structure

(1) Secondary structure of HIV-2 Vpx

Here, we visualize the secondary structure of HIV-2 Vpx using PDBSum (PDB code: 4CC9)



(2) Tertiary structure of HIV-2 Vpx

Here, we provide a structure movie of Vpx using PyMOL V1.7 (PDB code: 4CC9). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Localization

(1) Coding region of Vpx at the HIV genome


(2) Localization of Vpx during the HIV-2 life cycle

Here, we visualize the localization of Vpx during the viral life cycle. Red stars indicate the appearance of HIV-2 Vpx.


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-2 Vpx

Here, we visualize the drug binding pocket of HIV-2 Vpx



(2) List of known inhibitors targeting HIV-2 Vpx

Here, we summarize the published anti-HIV inhibitors which bind to HIV-2 Vpx.



Protein-protein interactions