Function of HIV Tat

  • Tat exists in all lentiviruses and is the first eukaryotic transcription factor known to interact with TAR (transactivating response element) in RNA instead of DNA [1].

  • Tat activates the transcription initiation and elongation of HIV-1 LTR promoter, preventing the premature termination of transcription and polyadenylation.

  • Tat acts as a nucleic acid chaperone to regulate the capping of HIV-1 mRNA[1].

  • Tat induces the T cell apoptosis, neurodegeneration and oxidative stress[1,2,3].

  • Tat regulates the expression of major histocompatibility complex (MHC) and downregulates several cell surface receptors [1,2,3].

  • Tat suppresses the activity of reverse transcriptase to prevent the premature synthesis of viral DNA [1,2,3].

  • Extracellular Tat upregulates the CXCR4 expression on CD4+ T cells, stimulates the expression of cytokines and interacts with cell-surface receptors to activate cellular signal transduction pathways. Tat is not incorporated in the viral particles [1,2,3].

Reference

  1. Xue B, Mizianty MJ, Kurgan L, Uversky VN: Protein intrinsic disorder as a flexible armor and a weapon of HIV-1. Cellular and molecular life sciences : CMLS 2012, 69(8):1211-1259.(Download Article)

  2. Strebel K: Virus-host interactions: role of HIV proteins Vif, Tat, and Rev. Aids 2003, 17 Suppl 4:S25-34.(Download Article)

  3. Brady J, Kashanchi F: Tat gets the "green" light on transcription initiation. Retrovirology 2005, 2:69.(Download Article)

Sequence

(1) Reference sequence for HIV-1 Tat

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

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  MEPVDPRLEP WKHPGSQPKT ACTNCYCKKC CFHCQVCFIT KALGISYGRK 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  KRRQRRRAHQ NSQTHQASLS KQPTSQPRGD PTGPKE*KKK VERETETDPF 
  101
  |
  D

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

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence: 

  1       10         20         30         40         50
  |        |          |          |          |          | 
  METPLREQEN SLESSNERSS CISEADASTP ESANLGEEIL SQLYRPLEAC 
  51      60         70         80         90         100
  |        |          |          |          |          | 
  YNTCYCKKCC YHCQFCFLKK GLGICYEQSR KRRRTPKKAK ANTSSASNKP 
  101    110        120        130
  |        |          |          | 
  ISNRTRHCQP EKAKKETVEK AVATAPGLGR

(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 Tat

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

Visualization

Our sequence dataset of HIV-1 subtype B Tat 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.

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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 Tat

Here, we visualize the secondary structure of HIV-1 Tat using PDBSum (PDB code: 1K5K)



(2) Tertiary structure of HIV-1 Tat

Here, we provide a structure movie of Tat using PyMOL V1.7 (PDB code: 1K5K). Alpha-helix and beta-strand secondary structures are demonstrated by red .

Localization

(1) Coding region of Tat at the HIV genome


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

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


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Tat

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



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

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



Protein-protein interactions