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Home / Equine Research Bank / J Virol / A minimal lentivirus Tat.
Journal of virology1991; 65(12); 7012-7015; doi: 10.1128/JVI.65.12.7012-7015.1991

A minimal lentivirus Tat.

Abstract: Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop.
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Publication Date: 1991-12-01 PubMed ID: 1658392PubMed Central: PMC250818DOI: 10.1128/JVI.65.12.7012-7015.1991Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the mechanisms of transcription regulation in lentiviruses, focusing on the roles of Tat effector proteins and TAR elements. Researchers identified the minimal lentivirus Tat as consisting of 25 amino acids, which play a crucial role in altering viral transcription and binding target RNA.

Understanding Lentivirus Transcription Mechanisms

  • Lentiviruses, a group of retroviruses, use specific regulatory mechanisms during their transcriptional process. These mechanisms involve RNA enhancer elements known as trans-activation responsive (TAR) elements, which are essentially nascent RNA stem-loops.
  • TAR elements are primary targets of Tat effectors, special proteins encoded by the virus. When TAR and Tat interact, the processivity of transcription complexes increases, leading to more efficient copying of the virus genomes.

Research Method and Findings

  • The researchers wanted to identify the most crucial aspects of the Tat-TAR interaction. To do this, they selected peptide motifs from Tats of two distantly related lentiviruses, HIV-1 and EIAV, and attached them to the coat protein of bacteriophage R17.
  • These models were then tested on the long terminal repeat of EIAV. In this test scenario, the TAR was replaced by the R17 operator, which is the target of the coat protein.
  • This RNA-tethering mechanism allowed the researchers to accurately pinpoint the activation domains of the Tats from HIV-1 and EIAV to 47 and 15 amino acids, respectively, while the RNA-binding domains were mapped to 10 and 26 amino acids.
  • Consequently, it was discovered that a minimal lentivirus Tat consists of a total of 25 amino acids. Within this structure, 15 amino acids are responsible for modifying the transcription process of the virus, while the remaining 10 amino acids bind to the target RNA stem-loop.

Implications of the Research

  • Given the pivotal role of Tat proteins in viral replication, this research provides valuable insight into the development of potential therapeutic strategies against lentiviruses, including HIV.
  • Understanding the minimal structure of the TAR-binding Tat peptide may pave the way for future studies exploring potential methods of disrupting its function, which could inhibit viral replication.

Cite This Article

APA
Derse D, Carvalho M, Carroll R, Peterlin BM. (1991). A minimal lentivirus Tat. J Virol, 65(12), 7012-7015. https://doi.org/10.1128/JVI.65.12.7012-7015.1991

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 65
Issue: 12
Pages: 7012-7015

Researcher Affiliations

Derse, D
  • Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201.
Carvalho, M
    Carroll, R
      Peterlin, B M

        MeSH Terms

        • Amino Acid Sequence
        • Base Sequence
        • Binding Sites
        • Capsid / genetics
        • Enhancer Elements, Genetic
        • Gene Expression Regulation, Viral
        • Genes, tat
        • HIV-1 / genetics
        • Infectious Anemia Virus, Equine / genetics
        • Lentivirus / genetics
        • Molecular Sequence Data
        • Plasmids
        • RNA, Viral / genetics
        • Repetitive Sequences, Nucleic Acid
        • Sequence Homology, Nucleic Acid
        • Transcription, Genetic
        • Transcriptional Activation

        References

        This article includes 27 references
        1. Cullen BR. Human immunodeficiency virus as a prototypic complex retrovirus.. J Virol 1991 Mar;65(3):1053-6.
          pubmed: 1995941doi: 10.1128/JVI.65.3.1053-1056.1991google scholar: lookup
        2. Greenblatt J, Li J. The nusA gene protein of Escherichia coli. Its identification and a demonstration that it interacts with the gene N transcription anti-termination protein of bacteriophage lambda.. J Mol Biol 1981 Mar 25;147(1):11-23.
          pubmed: 6455533doi: 10.1016/0022-2836(81)90076-0google scholar: lookup
        3. Roy S, Delling U, Chen CH, Rosen CA, Sonenberg N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation.. Genes Dev 1990 Aug;4(8):1365-73.
          pubmed: 2227414doi: 10.1101/gad.4.8.1365google scholar: lookup
        4. Marciniak RA, Calnan BJ, Frankel AD, Sharp PA. HIV-1 Tat protein trans-activates transcription in vitro.. Cell 1990 Nov 16;63(4):791-802.
          pubmed: 2225077doi: 10.1016/0092-8674(90)90145-5google scholar: lookup
        5. Cullen BR. The HIV-1 Tat protein: an RNA sequence-specific processivity factor?. Cell 1990 Nov 16;63(4):655-7.
          pubmed: 2225069doi: 10.1016/0092-8674(90)90129-3google scholar: lookup
        6. Romaniuk PJ, Lowary P, Wu HN, Stormo G, Uhlenbeck OC. RNA binding site of R17 coat protein.. Biochemistry 1987 Mar 24;26(6):1563-8.
          pubmed: 3297131doi: 10.1021/bi00380a011google scholar: lookup
        7. Whalen W, Ghosh B, Das A. NusA protein is necessary and sufficient in vitro for phage lambda N gene product to suppress a rho-independent terminator placed downstream of nutL.. Proc Natl Acad Sci U S A 1988 Apr;85(8):2494-8.
          pubmed: 2965813doi: 10.1073/pnas.85.8.2494google scholar: lookup
        8. Selby MJ, Bain ES, Luciw PA, Peterlin BM. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat.. Genes Dev 1989 Apr;3(4):547-58.
          pubmed: 2470647doi: 10.1101/gad.3.4.547google scholar: lookup
        9. Sadaie MR, Benter T, Wong-Staal F. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1.. Science 1988 Feb 19;239(4842):910-3.
          pubmed: 3277284doi: 10.1126/science.3277284google scholar: lookup
        10. Kao SY, Calman AF, Luciw PA, Peterlin BM. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product.. Nature 1987 Dec 3-9;330(6147):489-93.
          pubmed: 2825027doi: 10.1038/330489a0google scholar: lookup
        11. Roberts JW. Phage lambda and the regulation of transcription termination.. Cell 1988 Jan 15;52(1):5-6.
          pubmed: 2449971doi: 10.1016/0092-8674(88)90523-5google scholar: lookup
        12. Kawakami T, Sherman L, Dahlberg J, Gazit A, Yaniv A, Tronick SR, Aaronson SA. Nucleotide sequence analysis of equine infectious anemia virus proviral DNA.. Virology 1987 Jun;158(2):300-12.
          pubmed: 3035786doi: 10.1016/0042-6822(87)90202-9google scholar: lookup
        13. Berkhout B, Jeang KT. trans activation of human immunodeficiency virus type 1 is sequence specific for both the single-stranded bulge and loop of the trans-acting-responsive hairpin: a quantitative analysis.. J Virol 1989 Dec;63(12):5501-4.
          pubmed: 2479775doi: 10.1128/JVI.63.12.5501-5504.1989google scholar: lookup
        14. Frankel AD, Biancalana S, Hudson D. Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1.. Proc Natl Acad Sci U S A 1989 Oct;86(19):7397-401.
          pubmed: 2552444doi: 10.1073/pnas.86.19.7397google scholar: lookup
        15. Dingwall C, Ernberg I, Gait MJ, Green SM, Heaphy S, Karn J, Lowe AD, Singh M, Skinner MA. HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure.. EMBO J 1990 Dec;9(12):4145-53.
          pubmed: 2249668doi: 10.1002/j.1460-2075.1990.tb07637.xgoogle scholar: lookup
        16. Carvalho M, Derse D. Mutational analysis of the equine infectious anemia virus Tat-responsive element.. J Virol 1991 Jul;65(7):3468-74.
          pubmed: 1645778doi: 10.1128/JVI.65.7.3468-3474.1991google scholar: lookup
        17. Carroll R, Martarano L, Derse D. Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras.. J Virol 1991 Jul;65(7):3460-7.
          pubmed: 1645777doi: 10.1128/JVI.65.7.3460-3467.1991google scholar: lookup
        18. Calnan BJ, Biancalana S, Hudson D, Frankel AD. Analysis of arginine-rich peptides from the HIV Tat protein reveals unusual features of RNA-protein recognition.. Genes Dev 1991 Feb;5(2):201-10.
          pubmed: 1899841doi: 10.1101/gad.5.2.201google scholar: lookup
        19. Rosen CA. Regulation of HIV gene expression by RNA-protein interactions.. Trends Genet 1991 Jan;7(1):9-14.
          pubmed: 2003337doi: 10.1016/0168-9525(91)90015-igoogle scholar: lookup
        20. Gaynor R, Soultanakis E, Kuwabara M, Garcia J, Sigman DS. Specific binding of a HeLa cell nuclear protein to RNA sequences in the human immunodeficiency virus transactivating region.. Proc Natl Acad Sci U S A 1989 Jul;86(13):4858-62.
          pubmed: 2544877doi: 10.1073/pnas.86.13.4858google scholar: lookup
        21. Green M, Ishino M, Loewenstein PM. Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression.. Cell 1989 Jul 14;58(1):215-23.
          pubmed: 2752420doi: 10.1016/0092-8674(89)90417-0google scholar: lookup
        22. Feng S, Holland EC. HIV-1 tat trans-activation requires the loop sequence within tar.. Nature 1988 Jul 14;334(6178):165-7.
          pubmed: 3386755doi: 10.1038/334165a0google scholar: lookup
        23. Dorn P, DaSilva L, Martarano L, Derse D. Equine infectious anemia virus tat: insights into the structure, function, and evolution of lentivirus trans-activator proteins.. J Virol 1990 Apr;64(4):1616-24.
          pubmed: 2157047doi: 10.1128/JVI.64.4.1616-1624.1990google scholar: lookup
        24. Selby MJ, Peterlin BM. Trans-activation by HIV-1 Tat via a heterologous RNA binding protein.. Cell 1990 Aug 24;62(4):769-76.
          pubmed: 2117500doi: 10.1016/0092-8674(90)90121-tgoogle scholar: lookup
        25. Weeks KM, Ampe C, Schultz SC, Steitz TA, Crothers DM. Fragments of the HIV-1 Tat protein specifically bind TAR RNA.. Science 1990 Sep 14;249(4974):1281-5.
          pubmed: 2205002doi: 10.1126/science.2205002google scholar: lookup
        26. Marciniak RA, Garcia-Blanco MA, Sharp PA. Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus.. Proc Natl Acad Sci U S A 1990 May;87(9):3624-8.
          pubmed: 2333305doi: 10.1073/pnas.87.9.3624google scholar: lookup
        27. Pavlakis GN, Felber BK. Regulation of expression of human immunodeficiency virus.. New Biol 1990 Jan;2(1):20-31.
          pubmed: 2078551

        Citations

        This article has been cited 26 times.
        1. de Almeida SM, Rotta I, Vidal LRR, Dos Santos JS, Nath A, Johnson K, Letendre S, Ellis RJ. HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil.. J Neurovirol 2021 Feb;27(1):126-136.
          doi: 10.1007/s13365-020-00935-zpubmed: 33462791google scholar: lookup
        2. Gaskill PJ, Miller DR, Gamble-George J, Yano H, Khoshbouei H. HIV, Tat and dopamine transmission.. Neurobiol Dis 2017 Sep;105:51-73.
          doi: 10.1016/j.nbd.2017.04.015pubmed: 28457951google scholar: lookup
        3. Kukkonen S, Martinez-Viedma Mdel P, Kim N, Manrique M, Aldovini A. HIV-1 Tat second exon limits the extent of Tat-mediated modulation of interferon-stimulated genes in antigen presenting cells.. Retrovirology 2014 Apr 17;11:30.
          doi: 10.1186/1742-4690-11-30pubmed: 24742347google scholar: lookup
        4. 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 Apr;69(8):1211-59.
          doi: 10.1007/s00018-011-0859-3pubmed: 22033837google scholar: lookup
        5. Wang H, Ma X, Yeh YS, Zhu Y, Daugherty MD, Frankel AD, Musier-Forsyth K, Barbara PF. Comparative analysis of RNA/protein dynamics for the arginine-rich-binding motif and zinc-finger-binding motif proteins encoded by HIV-1.. Biophys J 2010 Nov 17;99(10):3454-62.
          doi: 10.1016/j.bpj.2010.09.051pubmed: 21081095google scholar: lookup
        6. Pantano S, Tyagi M, Giacca M, Carloni P. Molecular dynamics simulations on HIV-1 Tat.. Eur Biophys J 2004 Jul;33(4):344-51.
          doi: 10.1007/s00249-003-0358-zpubmed: 14608449google scholar: lookup
        7. Taube R, Fujinaga K, Irwin D, Wimmer J, Geyer M, Peterlin BM. Interactions between equine cyclin T1, Tat, and TAR are disrupted by a leucine-to-valine substitution found in human cyclin T1.. J Virol 2000 Jan;74(2):892-8.
          doi: 10.1128/jvi.74.2.892-898.2000pubmed: 10623752google scholar: lookup
        8. Filikov AV, James TL. Structure-based design of ligands for protein basic domains: application to the HIV-1 Tat protein.. J Comput Aided Mol Des 1998 May;12(3):229-40.
          doi: 10.1023/a:1007949625270pubmed: 9749367google scholar: lookup
        9. Orsini MJ, Debouck CM. Inhibition of human immunodeficiency virus type 1 and type 2 Tat function by transdominant Tat protein localized to both the nucleus and cytoplasm.. J Virol 1996 Nov;70(11):8055-63.
          doi: 10.1128/JVI.70.11.8055-8063.1996pubmed: 8892930google scholar: lookup
        10. Schafer SL, Vlach J, Pitha PM. Cooperation between herpes simplex virus type 1-encoded ICP0 and Tat to support transcription of human immunodeficiency virus type 1 long terminal repeat in vivo can occur in the absence of the TAR binding site.. J Virol 1996 Oct;70(10):6937-46.
          doi: 10.1128/JVI.70.10.6937-6946.1996pubmed: 8794337google scholar: lookup
        11. Carruth LM, Morse BA, Clements JE. The leucine domain of the visna virus Tat protein mediates targeting to an AP-1 site in the viral long terminal repeat.. J Virol 1996 Jul;70(7):4338-44.
          doi: 10.1128/JVI.70.7.4338-4344.1996pubmed: 8676456google scholar: lookup
        12. Tan W, Schalling M, Zhao C, Luukkonen M, Nilsson M, Fenyö EM, Pavlakis GN, Schwartz S. Inhibitory activity of the equine infectious anemia virus major 5' splice site in the absence of Rev.. J Virol 1996 Jun;70(6):3645-58.
          doi: 10.1128/JVI.70.6.3645-3658.1996pubmed: 8648699google scholar: lookup
        13. Mikovits JA, Hoffman PM, Rethwilm A, Ruscetti FW. In vitro infection of primary and retrovirus-infected human leukocytes by human foamy virus.. J Virol 1996 May;70(5):2774-80.
          doi: 10.1128/JVI.70.5.2774-2780.1996pubmed: 8627751google scholar: lookup
        14. Luo Y, Peterlin BM. Juxtaposition between activation and basic domains of human immunodeficiency virus type 1 Tat is required for optimal interactions between Tat and TAR.. J Virol 1993 Jun;67(6):3441-5.
          doi: 10.1128/JVI.67.6.3441-3445.1993pubmed: 8497060google scholar: lookup
        15. Madore SJ, Cullen BR. Genetic analysis of the cofactor requirement for human immunodeficiency virus type 1 Tat function.. J Virol 1993 Jul;67(7):3703-11.
          doi: 10.1128/JVI.67.7.3703-3711.1993pubmed: 8389901google scholar: lookup
        16. Carroll R, Derse D. Translation of equine infectious anemia virus bicistronic tat-rev mRNA requires leaky ribosome scanning of the tat CTG initiation codon.. J Virol 1993 Mar;67(3):1433-40.
          doi: 10.1128/JVI.67.3.1433-1440.1993pubmed: 8382305google scholar: lookup
        17. Alonso A, Cujec TP, Peterlin BM. Effects of human chromosome 12 on interactions between Tat and TAR of human immunodeficiency virus type 1.. J Virol 1994 Oct;68(10):6505-13.
          doi: 10.1128/JVI.68.10.6505-6513.1994pubmed: 8083988google scholar: lookup
        18. Carruth LM, Hardwick JM, Morse BA, Clements JE. Visna virus Tat protein: a potent transcription factor with both activator and suppressor domains.. J Virol 1994 Oct;68(10):6137-46.
          doi: 10.1128/JVI.68.10.6137-6146.1994pubmed: 8083955google scholar: lookup
        19. Mujeeb A, Bishop K, Peterlin BM, Turck C, Parslow TG, James TL. NMR structure of a biologically active peptide containing the RNA-binding domain of human immunodeficiency virus type 1 Tat.. Proc Natl Acad Sci U S A 1994 Aug 16;91(17):8248-52.
          doi: 10.1073/pnas.91.17.8248pubmed: 8058789google scholar: lookup
        20. Southgate CD, Green MR. Delineating minimal protein domains and promoter elements for transcriptional activation by lentivirus Tat proteins.. J Virol 1995 Apr;69(4):2605-10.
          doi: 10.1128/JVI.69.4.2605-2610.1995pubmed: 7884911google scholar: lookup
        21. Herrmann CH, Rice AP. Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor.. J Virol 1995 Mar;69(3):1612-20.
          doi: 10.1128/JVI.69.3.1612-1620.1995pubmed: 7853496google scholar: lookup
        22. Harmache A, Vitu C, Russo P, Bouyac M, Hieblot C, Peveri P, Vigne R, Suzan M. The caprine arthritis encephalitis virus tat gene is dispensable for efficient viral replication in vitro and in vivo.. J Virol 1995 Sep;69(9):5445-54.
          doi: 10.1128/JVI.69.9.5445-5454.1995pubmed: 7636990google scholar: lookup
        23. Hoffman DW, White SW. NMR analysis of the trans-activation response (TAR) RNA element of equine infectious anemia virus.. Nucleic Acids Res 1995 Oct 25;23(20):4058-65.
          doi: 10.1093/nar/23.20.4058pubmed: 7479065google scholar: lookup
        24. Alonso A, Derse D, Peterlin BM. Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells.. J Virol 1992 Jul;66(7):4617-21.
          doi: 10.1128/JVI.66.7.4617-4621.1992pubmed: 1602563google scholar: lookup
        25. Siderovski DP, Matsuyama T, Frigerio E, Chui S, Min X, Erfle H, Sumner-Smith M, Barnett RW, Mak TW. Random mutagenesis of the human immunodeficiency virus type-1 trans-activator of transcription (HIV-1 Tat).. Nucleic Acids Res 1992 Oct 25;20(20):5311-20.
          doi: 10.1093/nar/20.20.5311pubmed: 1437550google scholar: lookup
        26. Carroll R, Peterlin BM, Derse D. Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators.. J Virol 1992 Apr;66(4):2000-7.
          doi: 10.1128/JVI.66.4.2000-2007.1992pubmed: 1312617google scholar: lookup
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