hiv long terminal repeat


Summary: Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.

Top Publications

  1. Blazkova J, Trejbalova K, Gondois Rey F, Halfon P, Philibert P, Guiguen A, et al. CpG methylation controls reactivation of HIV from latency. PLoS Pathog. 2009;5:e1000554 pubmed publisher
    ..Tight but incomplete control of HIV-1 latency by CpG methylation might have important implications for strategies aimed at eradicating HIV-1 infection...
  2. Van Melckebeke H, Devany M, Di Primo C, Beaurain F, Toulmé J, Bryce D, et al. Liquid-crystal NMR structure of HIV TAR RNA bound to its SELEX RNA aptamer reveals the origins of the high stability of the complex. Proc Natl Acad Sci U S A. 2008;105:9210-5 pubmed publisher
  3. Wu X, Ishaq M, Hu J, Guo D. HCV NS3/4A protein activates HIV-1 transcription from its long terminal repeat. Virus Res. 2008;135:155-60 pubmed publisher
    ..These results have provided insights into the mechanism involved in the co-infection of HCV and HIV...
  4. Neogi U, Sood V, Goel N, Wanchu A, Banerjea A. Novel HIV-1 long terminal repeat (LTR) sequences of subtype B and mosaic intersubtype B/C recombinants in North India. Arch Virol. 2008;153:1961-6 pubmed publisher
    ..This is the first study to show a dominance of unique subtype B-LTRs and strongly suggests that this region could also be a hot spot for the formation of highly complex inter subtype B/C recombinants. ..
  5. Rodriguez M, Shen C, Ratner D, Paranjape R, Kulkarni S, Chatterjee R, et al. Genetic and functional characterization of the LTR of HIV-1 subtypes A and C circulating in India. AIDS Res Hum Retroviruses. 2007;23:1428-33 pubmed publisher
    ..To our knowledge, this is the first study characterizing the genetic structure and functional attributes of subtype A LTRs from India. ..
  6. Egelé C, Piemont E, Didier P, Ficheux D, Roques B, Darlix J, et al. The single-finger nucleocapsid protein of moloney murine leukemia virus binds and destabilizes the TAR sequences of HIV-1 but does not promote efficiently their annealing. Biochemistry. 2007;46:14650-62 pubmed
    ..Due to its ability to mimic NCp7, the simple structure of NCp10 might be useful to design peptidomimetics aimed at inhibiting HIV replication. ..
  7. Lu J, Kadakkuzha B, Zhao L, Fan M, Qi X, Xia T. Dynamic ensemble view of the conformational landscape of HIV-1 TAR RNA and allosteric recognition. Biochemistry. 2011;50:5042-57 pubmed publisher
    ..A dynamic model of the ensemble view of the conformational landscape for HIV-1 TAR RNA is proposed, and the implication of the general mechanism of RNA recognition and its impact on RNA-based therapeutics are discussed. ..
  8. Davidson A, Begley D, Lau C, Varani G. A small-molecule probe induces a conformation in HIV TAR RNA capable of binding drug-like fragments. J Mol Biol. 2011;410:984-96 pubmed publisher
    ..These models further suggest linking strategies for the development of higher-affinity lead compounds for the inhibition of the TAR-Tat interaction. ..
  9. Sedore S, Byers S, Biglione S, Price J, Maury W, Price D. Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR. Nucleic Acids Res. 2007;35:4347-58 pubmed
    ..This suggests that in the absence of Tat, HEXIM1 may bind to TAR and repress transcription elongation of the HIV LTR. ..

More Information


  1. Kumar S, Kellish P, Robinson W, Wang D, Appella D, Arya D. Click dimers to target HIV TAR RNA conformation. Biochemistry. 2012;51:2331-47 pubmed publisher
    ..Cytopathic effects investigated using MT-2 cells indicate a number of the dimers with high affinity toward TAR show promising anti-HIV activity. ..
  2. Reigadas S, Andreola M, Wittkop L, Cosnefroy O, Anies G, Recordon Pinson P, et al. Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir-treated patients and in in vitro infected cells. J Antimicrob Chemother. 2010;65:434-7 pubmed publisher
    ..The frequent rearrangements found in 2-LTR sequences warrant further investigations to determine the dynamics of evolution of unintegrated HIV-1 DNA. ..
  3. Frank A, Stelzer A, Al Hashimi H, Andricioaei I. Constructing RNA dynamical ensembles by combining MD and motionally decoupled NMR RDCs: new insights into RNA dynamics and adaptive ligand recognition. Nucleic Acids Res. 2009;37:3670-9 pubmed publisher
  4. Zargarian L, Kanevsky I, Bazzi A, Boynard J, Chaminade F, Fosse P, et al. Structural and dynamic characterization of the upper part of the HIV-1 cTAR DNA hairpin. Nucleic Acids Res. 2009;37:4043-54 pubmed publisher
  5. Davidson A, Leeper T, Athanassiou Z, Patora Komisarska K, Karn J, Robinson J, et al. Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic peptide mimics of Tat protein. Proc Natl Acad Sci U S A. 2009;106:11931-6 pubmed publisher
    ..It also provides insight into the P-TEFb binding site and a rational basis for optimizing the promising antiviral activity observed for these cyclic peptides. ..
  6. Wagschal A, Rousset E, Basavarajaiah P, Contreras X, Harwig A, Laurent Chabalier S, et al. Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII. Cell. 2012;150:1147-57 pubmed publisher
    ..Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation. ..
  7. Klase Z, Winograd R, Davis J, Carpio L, Hildreth R, Heydarian M, et al. HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression. Retrovirology. 2009;6:18 pubmed publisher
  8. Vo M, Barany G, Rouzina I, Musier Forsyth K. HIV-1 nucleocapsid protein switches the pathway of transactivation response element RNA/DNA annealing from loop-loop "kissing" to "zipper". J Mol Biol. 2009;386:789-801 pubmed publisher
  9. Berg R, Aggerholm A, Bertelsen L, Østergaard L, Paludan S. Role of mitogen-activated protein kinases, nuclear factor-kappaB, and interferon regulatory factor 3 in Toll-like receptor 4-mediated activation of HIV long terminal repeat. APMIS. 2009;117:124-32 pubmed publisher
    ..Neither of the mitogen-activated protein kinases ERK1/2, JNK, or p38 nor the transcription factor interferon regulatory factor 3 were involved in the direct transactivation of HIV-LTR through stimulation of TLR4. ..
  10. Sung T, Rice A. miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1. PLoS Pathog. 2009;5:e1000263 pubmed publisher
    ..Our data indicate that miR-198 functions to restrict HIV-1 replication in monocytes, and its mechanism of action appears to involve repression of Cyclin T1 expression. ..
  11. Bardaro M, Shajani Z, Patora Komisarska K, Robinson J, Varani G. How binding of small molecule and peptide ligands to HIV-1 TAR alters the RNA motional landscape. Nucleic Acids Res. 2009;37:1529-40 pubmed publisher
    ..However, the new cyclic peptide mimic of Tat represents a new class of ligands with a unique effect on the dynamics and the structure of the apical loop. ..
  12. Pagans S, Kauder S, Kaehlcke K, Sakane N, Schroeder S, Dormeyer W, et al. The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription. Cell Host Microbe. 2010;7:234-44 pubmed publisher
    ..Our findings uncover a positive role for Set7/9-KMT7 and Tat methylation during early steps of the Tat transactivation cycle. ..
  13. Aagaard L, Zhang J, von Eije K, Li H, Saetrom P, Amarzguioui M, et al. Engineering and optimization of the miR-106b cluster for ectopic expression of multiplexed anti-HIV RNAs. Gene Ther. 2008;15:1536-49 pubmed publisher
  14. Pyo C, Yang Y, Yoo N, Choi S. Reactive oxygen species activate HIV long terminal repeat via post-translational control of NF-kappaB. Biochem Biophys Res Commun. 2008;376:180-5 pubmed publisher
    ..In this study, we demonstrate that H2O2 treatment strongly induced HIV long terminal repeat (LTR)-driven luciferase expression in Jurkat T lymphocytes via NF-kappaB activation...
  15. Dash P, Siddappa N, Mangaiarkarasi A, Mahendarkar A, Roshan P, Anand K, et al. Exceptional molecular and coreceptor-requirement properties of molecular clones isolated from an Human Immunodeficiency Virus Type-1 subtype C infection. Retrovirology. 2008;5:25 pubmed publisher
    ..The exceptional biological and molecular properties of these clones make them invaluable tools to understand the unique pathogenic characteristics of subtype C. ..
  16. Buzon M, Massanella M, Llibre J, Esteve A, Dahl V, Puertas M, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16:460-5 pubmed publisher
    ..The ability of raltegravir intensification to perturb the reservoir that supports active replication has implications for therapeutic strategies aimed at achieving viral eradication. ..
  17. Darfeuille F, Reigadas S, Hansen J, Orum H, Di Primo C, Toulmé J. Aptamers targeted to an RNA hairpin show improved specificity compared to that of complementary oligonucleotides. Biochemistry. 2006;45:12076-82 pubmed
    ..These results demonstrate the benefit of reading the three-dimensional shape of an RNA target rather than its primary sequence for the design of highly specific oligonucleotides. ..
  18. Musselman C, Pitt S, Gulati K, Foster L, Andricioaei I, Al Hashimi H. Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings. J Biomol NMR. 2006;36:235-49 pubmed
    ..Results confirm earlier findings that the two TAR helices undergo large changes in both their mean relative orientation and dynamics upon binding to different targets. ..
  19. Klase Z, Kale P, Winograd R, Gupta M, Heydarian M, Berro R, et al. HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR. BMC Mol Biol. 2007;8:63 pubmed
    ..HIV-1 TAR element is processed by the Dicer enzyme to create a viral miRNA. This viral miRNA is detectable in infected cells and appears to contribute to viral latency. ..
  20. Ludwig L, Ambrus J, Krawczyk K, Sharma S, Brooks S, Hsiao C, et al. Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products. Retrovirology. 2006;3:80 pubmed
    ..The novel HAPs are encoded in a region of the LTR that has already been shown to be deleted in some HIV-infected long-term survivors and represent new potential targets for vaccine development. ..
  21. Molle D, Maiuri P, Boireau S, Bertrand E, Knezevich A, Marcello A, et al. A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites. Retrovirology. 2007;4:36 pubmed
  22. Rafati H, Parra M, Hakre S, Moshkin Y, Verdin E, Mahmoudi T. Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency. PLoS Biol. 2011;9:e1001206 pubmed publisher
    ..Our data point to the ATP-dependent BRG1 component of BAF as a putative therapeutic target to deplete the latent reservoir in patients. ..
  23. Pachulska Wieczorek K, Purzycka K, Adamiak R. New, extended hairpin form of the TAR-2 RNA domain points to the structural polymorphism at the 5' end of the HIV-2 leader RNA. Nucleic Acids Res. 2006;34:2984-97 pubmed
    ..We propose that an internal loop region of the TAR-2 extended hairpin form is a potential Tat-2 binding site. ..
  24. Wang D, Iera J, Baker H, Hogan P, Ptak R, Yang L, et al. Multivalent binding oligomers inhibit HIV Tat-TAR interaction critical for viral replication. Bioorg Med Chem Lett. 2009;19:6893-7 pubmed publisher
    ..Antiviral studies are also consistent with the in vitro and cell-based assays. MBOs provide a framework for the development of future RNA-targeting molecules. ..
  25. Henderson L, Narasipura S, Adarichev V, Kashanchi F, Al Harthi L. Identification of novel T cell factor 4 (TCF-4) binding sites on the HIV long terminal repeat which associate with TCF-4, ?-catenin, and SMAR1 to repress HIV transcription. J Virol. 2012;86:9495-503 pubmed publisher
    ..TCF-4 binding sites at -336, -143, +66, and +186 relative to the transcription initiation site on the HIV long terminal repeat (LTR). Two of the sites (-143 and +66) were present in approximately 1/3 of 500 HIV-1 isolates examined...
  26. Bernhard W, Barreto K, Saunders A, Dahabieh M, Johnson P, Sadowski I. The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response. FEBS Lett. 2011;585:3549-54 pubmed publisher
    ..These results indicate that chaetocin may provide a therapy to purge cells of latent HIV-1, possibly in combination with other chromatin remodeling drugs. ..
  27. van der Sluis R, Pollakis G, van Gerven M, Berkhout B, Jeeninga R. Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter. Retrovirology. 2011;8:73 pubmed publisher
    ..This subtype AE property is related to the presence of a GABP instead of NF?B binding site in the LTR. ..
  28. Bailor M, Sun X, Al Hashimi H. Topology links RNA secondary structure with global conformation, dynamics, and adaptation. Science. 2010;327:202-6 pubmed publisher
  29. Matreyek K, Engelman A. The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J Virol. 2011;85:7818-27 pubmed publisher
    ..These results suggest that capsid, likely by the qualities of its uncoating, determines whether HIV-1 requires cellular NUP153 for PIC nuclear import. ..
  30. Huber K, Doyon G, Plaks J, Fyne E, Mellors J, Sluis Cremer N. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J Biol Chem. 2011;286:22211-8 pubmed publisher
    ..Taken together, our study suggests an important role for HDAC3 in HIV-1 latency and, importantly, describes a chemical approach that can readily be used to identify the HDAC isoforms that contribute to HIV-1 latency in other cell types. ..
  31. Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. J Biol Chem. 2013;288:20014-33 pubmed publisher
    ..Taken together, our experiments demonstrated that HIV-1-infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS. ..
  32. Rawat P, Mitra D. Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways. Nucleic Acids Res. 2011;39:5879-92 pubmed publisher
    ..Thus, the present work not only identifies a molecular basis for HSF1-mediated enhancement of viral replication but also provides another example of how HIV-1 uses host cell machinery for its successful replication in the host. ..
  33. Langley D, Samanta H, Lin Z, Walker M, Krystal M, Dicker I. The terminal (catalytic) adenosine of the HIV LTR controls the kinetics of binding and dissociation of HIV integrase strand transfer inhibitors. Biochemistry. 2008;47:13481-8 pubmed publisher
    ..These findings further our understanding of the details of the inhibitor binding site of specific strand transfer inhibitors. ..
  34. Malcolm T, Kam J, Pour P, Sadowski I. Specific interaction of TFII-I with an upstream element on the HIV-1 LTR regulates induction of latent provirus. FEBS Lett. 2008;582:3903-8 pubmed publisher
    ..These results demonstrate an essential role of TFII-I bound at an upstream LTR element for viral replication. ..
  35. Centlivre M, Klaver B, Berkhout B, Das A. Functional analysis of the complex trans-activating response element RNA structure in simian immunodeficiency virus. J Virol. 2008;82:9171-8 pubmed publisher
    ..These results demonstrate that the complex TAR structure in SIVmac has no other essential function in virus replication in vitro besides its role in Tat-mediated activation of transcription. ..
  36. du Chéné I, Basyuk E, Lin Y, Triboulet R, Knezevich A, Chable Bessia C, et al. Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 2007;26:424-35 pubmed
    ..Finally, we show in different cellular models, including PBMCs from HIV-1-infected donors, that HIV-1 reactivation could be achieved after HP1gamma RNA interference. ..
  37. Lassot I, Latreille D, Rousset E, Sourisseau M, Linares L, Chable Bessia C, et al. The proteasome regulates HIV-1 transcription by both proteolytic and nonproteolytic mechanisms. Mol Cell. 2007;25:369-83 pubmed
    ..19S components facilitated transcriptional elongation and may be involved in clearance of paused transcriptional elongation complexes from the promoter. ..
  38. Pan C, Mezei M, Mujtaba S, Muller M, Zeng L, Li J, et al. Structure-guided optimization of small molecules inhibiting human immunodeficiency virus 1 Tat association with the human coactivator p300/CREB binding protein-associated factor. J Med Chem. 2007;50:2285-8 pubmed
  39. Sarkar I, Hauber I, Hauber J, Buchholz F. HIV-1 proviral DNA excision using an evolved recombinase. Science. 2007;316:1912-5 pubmed
    ..Although a long way from use in the clinic, we speculate that this type of technology might be adapted in future antiretroviral therapies, among other possible uses. ..
  40. Lebars I, Richard T, Di Primo C, Toulmé J. NMR structure of a kissing complex formed between the TAR RNA element of HIV-1 and a LNA-modified aptamer. Nucleic Acids Res. 2007;35:6103-14 pubmed
    ..Our data also showed that the introduction of LNA residues provides an enhanced stability while maintaining a normal Watson-Crick base pairing with a loop-loop conformation close to an A-type. ..
  41. Wang Y, Rice A. Interleukin-10 inhibits HIV-1 LTR-directed gene expression in human macrophages through the induction of cyclin T1 proteolysis. Virology. 2006;352:485-92 pubmed
    ..Together, these results suggest that the down-regulation of cyclin T1, and consequently Tat function, contributes to the suppressive effect of IL-10 on HIV-1 replication in human macrophages. ..
  42. Salmon L, Bascom G, Andricioaei I, Al Hashimi H. A general method for constructing atomic-resolution RNA ensembles using NMR residual dipolar couplings: the basis for interhelical motions revealed. J Am Chem Soc. 2013;135:5457-66 pubmed publisher
    ..This new approach broadens the scope of using RDCs in characterizing the dynamics of nucleic acids. ..
  43. Provost P, Barat C, Plante I, Tremblay M. HIV-l and the microRNA-guided silencing pathway: an intricate and multifaceted encounter. Virus Res. 2006;121:107-15 pubmed
    ..As we learn more about the mechanism and importance of small RNA-based antiviral systems, a more intricate picture of the interaction between HIV-1 and a proven antiviral defense mechanism in lower eukaryotes is emerging. ..
  44. Ishida T, Hamano A, Koiwa T, Watanabe T. 5' long terminal repeat (LTR)-selective methylation of latently infected HIV-1 provirus that is demethylated by reactivation signals. Retrovirology. 2006;3:69 pubmed
    ..These results suggest that selective epigenetic modification of the 5'LTR of the HIV-1 provirus may be an important mechanism by which proviral activity is suppressed. ..
  45. Engelman A. AIDS/HIV. A reversal of fortune in HIV-1 integration. Science. 2007;316:1855-7 pubmed
  46. Jiang G, Espeseth A, Hazuda D, Margolis D. c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J Virol. 2007;81:10914-23 pubmed
    ..These results expand the understanding of mechanisms that recruit HDAC and maintain the latency of HIV-1, suggesting novel therapeutic approaches against latent proviral HIV infection. ..
  47. Neogi U, Sood V, Banerjee S, Ghosh N, Verma S, Samrat S, et al. Global HIV-1 molecular epidemiology with special reference to genetic analysis of HIV-1 subtypes circulating in North India: functional and pathogenic implications of genetic variation. Indian J Exp Biol. 2009;47:424-31 pubmed
    ..These differences may help in better understanding of unique features of HIV-1 epidemic in India. ..
  48. Olsen G, Echodu D, Shajani Z, Bardaro M, Varani G, Drobny G. Solid-state deuterium NMR studies reveal micros-ns motions in the HIV-1 transactivation response RNA recognition site. J Am Chem Soc. 2008;130:2896-7 pubmed publisher
  49. Weinberger L, Dar R, Simpson M. Transient-mediated fate determination in a transcriptional circuit of HIV. Nat Genet. 2008;40:466-70 pubmed publisher
    ..Thus, transcriptional positive feedback can modulate transient expression lifetime to a greater extent than protein half-life modulation, and it has a critical role in the cell-fate decision in HIV. ..
  50. Buchholz F, Hauber J. In vitro evolution and analysis of HIV-1 LTR-specific recombinases. Methods. 2011;53:102-9 pubmed publisher
    ..We furthermore provide protocols that are utilized for the investigation of Tre's antiretroviral activity in infected tissue cultures as well as in infected humanized Rag2(-/-)?c(-/-) mice. ..
  51. Singh A, Razooky B, Cox C, Simpson M, Weinberger L. Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression. Biophys J. 2010;98:L32-4 pubmed publisher
    ..These data indicate that transcriptional bursting can generate high variability in HIV-1 early gene products, which may critically influence the viral fate-decision between active replication and proviral latency. ..
  52. Sharma K, Didier P, Darlix J, de Rocquigny H, Bensikaddour H, Lavergne J, et al. Kinetic analysis of the nucleic acid chaperone activity of the hepatitis C virus core protein. Nucleic Acids Res. 2010;38:3632-42 pubmed publisher
    ..The three peptides operate similarly, confirming that the core chaperone properties are mostly supported by its basic clusters. ..
  53. Yang H, Shen L, Siliciano R, Pomerantz J. Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation. Proc Natl Acad Sci U S A. 2009;106:6321-6 pubmed publisher
    ..Our results highlight the therapeutic potential of cellular factors for the reactivation of latent HIV-1 and provide an efficient approach for their identification. ..