hiv 1 reverse transcriptase

Summary

Summary: HIV-1 enzyme responsible for the synthesis of DNA from genomic RNA of the virus. It exists as a heterodimer of a 66 kDa (p66) subunit and a 51 kDa (p51) subunit. It is encoded by the pol gene of HIV-1. EC 2.7.7.-.

Top Publications

  1. ncbi Efficient initiation of HIV-1 reverse transcription in vitro. Requirement for RNA sequences downstream of the primer binding site abrogated by nucleocapsid protein-dependent primer-template interactions
    Yasumasa Iwatani
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:14185-95. 2003
  2. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
  3. pmc Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7
    Ariberto Fassati
    The Wohl Virion Centre, Windeyer Institute, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK
    EMBO J 22:3675-85. 2003
  4. pmc Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H, and integrase activities by hydroxytropolones
    Joël Didierjean
    Unité Propre de Recherche 9002 du CNRS conventionnée à l Université Louis Pasteur, IBMC, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Antimicrob Agents Chemother 49:4884-94. 2005
  5. ncbi Resistance of HIV-1 to multiple antiretroviral drugs in France: a 6-year survey (1997-2002) based on an analysis of over 7000 genotypes
    Catherine Tamalet
    Laboratoire de Virologie, CHRU La Timone, 13005 Marseille, France
    AIDS 17:2383-8. 2003
  6. pmc Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1
    Michael J Hofman
    Center for Comparative Medicine, University of California, Davis, CA 95616, USA
    Antimicrob Agents Chemother 48:3483-90. 2004
  7. ncbi Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients
    Michael D Miller
    Gilead Sciences, Foster City, California 94404, USA
    J Infect Dis 189:837-46. 2004
  8. pmc Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer
    Johanna Wapling
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, GPO Box 2284, Melbourne, Victoria 3001, Australia
    J Virol 79:10247-57. 2005
  9. ncbi Differential susceptibility of HIV-1 reverse transcriptase to inhibition by RNA aptamers in enzymatic reactions monitoring specific steps during genome replication
    Daniel M Held
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    J Biol Chem 281:25712-22. 2006
  10. pmc Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase
    Lamei Chen
    Molecular Biology Institute, Center for Genomics and Proteomics, Dept of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095 1570, USA
    J Virol 78:3722-32. 2004

Research Grants

  1. Primate Model Towards HIV Eradication Strategies
    RAYMOND FELIX SCHINAZI; Fiscal Year: 2012
  2. Determinants of HIV Dynamics and Variation
    JOSE ORLANDO MALDONADO-ORTIZ; Fiscal Year: 2013
  3. Discovery of Novel HIV-1 Reverse Transcriptase Inhibitors by Fragment Screening
    ANGELA MCKOY; Fiscal Year: 2013
  4. Novel mechanisms of HIV resistance to RTIs
    NICOLAS P SLUIS-CREMER; Fiscal Year: 2012
  5. Rational Design of NRTI for Drug Resistant HIV-1
    John W Mellors; Fiscal Year: 2010
  6. Inhibitors of host kinases as molecular targets for immune defense against HIV-1
    Mathias Lichterfeld; Fiscal Year: 2013
  7. Molecular Recognition of Proteins and Ligand Design
    William L Jorgensen; Fiscal Year: 2013
  8. Mechanism and Regulation of HIV-1 Uncoating
    CHRISTOPHER R AIKEN; Fiscal Year: 2013
  9. Structual studies of HIV-1 integration
    Mamuka Kvaratskhelia; Fiscal Year: 2013
  10. HIV-1 reverse transcriptase structure: function, inhibition, and resistance
    EDWARD V ARNOLD; Fiscal Year: 2013

Detail Information

Publications194 found, 100 shown here

  1. ncbi Efficient initiation of HIV-1 reverse transcription in vitro. Requirement for RNA sequences downstream of the primer binding site abrogated by nucleocapsid protein-dependent primer-template interactions
    Yasumasa Iwatani
    Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:14185-95. 2003
    ..Taken together, this study leads to new insights into the initiation of HIV-1 reverse transcription and the functional role of NC-facilitated tRNA-template interactions in this process...
  2. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
    ..Sequence data on two new molecular targets of HIV drug therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003...
  3. pmc Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7
    Ariberto Fassati
    The Wohl Virion Centre, Windeyer Institute, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK
    EMBO J 22:3675-85. 2003
    ..These results provide a new insight into the molecular mechanism for HIV-1 nuclear import and reveal potential targets for therapeutic intervention...
  4. pmc Inhibition of human immunodeficiency virus type 1 reverse transcriptase, RNase H, and integrase activities by hydroxytropolones
    Joël Didierjean
    Unité Propre de Recherche 9002 du CNRS conventionnée à l Université Louis Pasteur, IBMC, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Antimicrob Agents Chemother 49:4884-94. 2005
    ..However, all tested compounds exhibited cellular toxicity that presently limits their applications...
  5. ncbi Resistance of HIV-1 to multiple antiretroviral drugs in France: a 6-year survey (1997-2002) based on an analysis of over 7000 genotypes
    Catherine Tamalet
    Laboratoire de Virologie, CHRU La Timone, 13005 Marseille, France
    AIDS 17:2383-8. 2003
    ..The aim of this study was to assess the extent of multiple drug resistance among individuals followed for HIV-1 infection in France...
  6. pmc Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1
    Michael J Hofman
    Center for Comparative Medicine, University of California, Davis, CA 95616, USA
    Antimicrob Agents Chemother 48:3483-90. 2004
    ..Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz...
  7. ncbi Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients
    Michael D Miller
    Gilead Sciences, Foster City, California 94404, USA
    J Infect Dis 189:837-46. 2004
    ..The results from these controlled clinical trials provide guidance for the use of tenofovir DF for treatment-experienced patients...
  8. pmc Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer
    Johanna Wapling
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, GPO Box 2284, Melbourne, Victoria 3001, Australia
    J Virol 79:10247-57. 2005
    ..The inhibition of RT activity is most likely due to a defect in RT maturation, suggesting that RT dimerization represents a valid drug target for chemotherapeutic intervention...
  9. ncbi Differential susceptibility of HIV-1 reverse transcriptase to inhibition by RNA aptamers in enzymatic reactions monitoring specific steps during genome replication
    Daniel M Held
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    J Biol Chem 281:25712-22. 2006
    ..Together, these results support a model wherein aptamers suppress viral replication by cumulative inhibition of RT at every stage of genome replication...
  10. pmc Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase
    Lamei Chen
    Molecular Biology Institute, Center for Genomics and Proteomics, Dept of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095 1570, USA
    J Virol 78:3722-32. 2004
    ..bioinformatics.ucla.edu/HIV. Our data indicate that positive selection mapping is an analysis that can yield powerful insights from high-throughput sequencing of rapidly mutating pathogens...
  11. pmc Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1
    Thomas W North
    Center for Comparative Medicine, University of California, Davis, CA 95616, USA
    J Virol 79:7349-54. 2005
    ..These results mimic HAART of HIV-1-infected humans. The RT-SHIV/rhesus macaque model should be useful for studies of tissue reservoirs and sites of residual replication that are not possible or practical with humans...
  12. ncbi Proteolytic processing of an HIV-1 pol polyprotein precursor: insights into the mechanism of reverse transcriptase p66/p51 heterodimer formation
    Nicolas Sluis-Cremer
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Scaife Hall, Suite S817, 350 Terrace Street, Pittsburgh, PA 15261, USA
    Int J Biochem Cell Biol 36:1836-47. 2004
    ..These results provide the first experimental data defining the pathway for the HIV-1 PR catalyzed formation of the p66/p51 HIV-1 RT heterodimer...
  13. ncbi Dimerization of human immunodeficiency virus type 1 reverse transcriptase as an antiviral target
    S Srivastava
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, Victoria 3004, Australia
    Curr Pharm Des 12:1879-94. 2006
    ....
  14. pmc Potent inhibition of human immunodeficiency virus type 1 replication by template analog reverse transcriptase inhibitors derived by SELEX (systematic evolution of ligands by exponential enrichment)
    Pheroze Joshi
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    J Virol 76:6545-57. 2002
    ..As virion-encapsidated TRTIs can predispose virions for inhibition immediately upon entry, they should prove to be efficacious agents in gene therapy approaches for AIDS...
  15. pmc A nucleotide substitution in the tRNA(Lys) primer binding site dramatically increases replication of recombinant simian immunodeficiency virus containing a human immunodeficiency virus type 1 reverse transcriptase
    Kelly Soderberg
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Virol 76:5803-6. 2002
    ..RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model...
  16. ncbi Modulation of HIV-1 replication by RNA interference
    Jean Marc Jacque
    Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA
    Nature 418:435-8. 2002
    ....
  17. ncbi Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy
    P Richard Harrigan
    British Columbia Centre for Excellence in HIV AIDS, and Department of Medicine, University of British Columbia, Vancouver, Canada
    J Infect Dis 191:339-47. 2005
    ....
  18. ncbi Evidence for positive epistasis in HIV-1
    Sebastian Bonhoeffer
    Ecology and Evolution, ETH Zurich, ETH Zentrum NW, CH 8092 Zurich, Switzerland
    Science 306:1547-50. 2004
    ..Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1...
  19. ncbi The annealing mechanism of HIV-1 reverse transcription primer onto the viral genome
    Carine Tisne
    Laboratoire de Cristallographie et Résonance Magnétique Nucléaire Biologiques, UMR 8015 CNRS, 4 avenue de l Observatoire, 75006 Paris, France
    J Biol Chem 279:3588-95. 2004
    ....
  20. pmc Mutations that confer resistance to template-analog inhibitors of human immunodeficiency virus (HIV) type 1 reverse transcriptase lead to severe defects in HIV replication
    Timothy S Fisher
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Virol 76:4068-72. 2002
    ..Therefore, viruses with such mutations are replication defective. Potent inhibition and a built-in mechanism to render aptamer-resistant viruses replication defective make this an attractive class of inhibitors...
  21. pmc tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes
    Lyubov Zaitseva
    1Wohl Virion Centre, London, United Kingdom
    PLoS Biol 4:e332. 2006
    ..Here we provide evidence that at least some tRNA species can be imported into the nucleus of human cells and promote HIV-1 nuclear import...
  22. pmc Forced selection of a human immunodeficiency virus type 1 variant that uses a non-self tRNA primer for reverse transcription: involvement of viral RNA sequences and the reverse transcriptase enzyme
    Truus E M Abbink
    Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    J Virol 78:10706-14. 2004
    ..We demonstrate that both the PAS and RT mutations improve the replication capacity of the tRNA(1,2)(Lys)-using virus...
  23. ncbi Antiretroviral resistance among HIV-infected persons who have died in British Columbia, in the era of modern antiretroviral therapy
    Magdalena A Recsky
    British Columbia Centre for Excellence in HIV AIDS, St Paul s Hospital, Vancouver, British Columbia, Canada
    J Infect Dis 190:285-92. 2004
    ....
  24. ncbi Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis
    John G Julias
    Basic Research Program, SAIC Frederick, Inc, NCI Frederick, Frederick, MD 21702 1201, USA
    Virology 322:13-21. 2004
    ..The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT...
  25. ncbi Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs)
    Valerie Goldschmidt
    Unité Propre de Recherche 9002 du CNRS conventionnée à l Université Louis Pasteur, IBMC, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Int J Biochem Cell Biol 36:1687-705. 2004
    ....
  26. ncbi Aptamers directed to HIV-1 reverse transcriptase display greater efficacy over small hairpin RNAs targeted to viral RNA in blocking HIV-1 replication
    Pheroze J Joshi
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, GB401, Bronx, NY 10461, USA
    Mol Ther 11:677-86. 2005
    ..Furthermore, anti-RT aptamers expressed in T cells afforded protection against high-dose infection by chimeric RT-SHIV viruses...
  27. ncbi Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness
    David R Bangsberg
    Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, San Francisco General Hospital, UCSF, San Francisco, California 94143 1372, USA
    AIDS 20:223-31. 2006
    ....
  28. pmc Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity
    Kirsten L White
    Gilead Sciences, Foster City, California 94404 ViroLogic, Inc, South San Francisco, California 94080, USA
    Antimicrob Agents Chemother 46:3437-46. 2002
    ....
  29. pmc Combinatorial selection, inhibition, and antiviral activity of DNA thioaptamers targeting the RNase H domain of HIV-1 reverse transcriptase
    Anoma Somasunderam
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555, USA
    Biochemistry 44:10388-95. 2005
    ..0005 to 0.05, with a reduction of the level of virus production by more than 50% at high moi. Suppression of virus was comparable to that seen with AZT when moi <or= 0.005...
  30. ncbi Thymidine analogue mutation profiles: factors associated with acquiring specific profiles and their impact on the virological response to therapy
    Alessandro Cozzi-Lepri
    Royal Free and University College Medical School, London, UK
    Antivir Ther 10:791-802. 2005
    ....
  31. ncbi Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study)
    Antonella Castagna
    Clinic of Infectious Diseases, Vita Salute San Raffaele University, Milan, Italy
    AIDS 20:795-803. 2006
    ..We compared the immunological and clinical outcomes of lamivudine monotherapy and complete therapy interruption in the treatment of HIV-1-infected patients harbouring lamivudine-resistant virus...
  32. pmc A hard way to the nucleus
    Michael Bukrinsky
    The George Washington University Medical Center, 2300 Eye Street NW, Ross Hall Room 734, Washington, DC 20037, USA
    Mol Med 10:1-5. 2004
    ..In this review, we will discuss recent advances and suggest possible solutions to the controversial issue of HIV-1 nuclear import...
  33. pmc Multiparameter single-molecule fluorescence spectroscopy reveals heterogeneity of HIV-1 reverse transcriptase:primer/template complexes
    P J Rothwell
    Abteilung Spektroskopie und Photochemische Kinetik, Max Planck Institut fur biophysikalische Chemie, Am Fassberg 11, D 37077 Gottingen, Germany
    Proc Natl Acad Sci U S A 100:1655-60. 2003
    ..The second RT:nucleic acid complex is the product state, which is formed immediately after nucleotide incorporation, but before RT translates to the next nucleotide...
  34. ncbi Learning multiple evolutionary pathways from cross-sectional data
    Niko Beerenwinkel
    Max Planck Institut für Informatik, Stuhlsatzenhausweg 85, D 66123 Saarbrucken, Germany
    J Comput Biol 12:584-98. 2005
    ..We obtain a generative probabilistic model for the development of drug resistance in HIV that agrees with biological knowledge. Further applications and extensions of the model are discussed...
  35. ncbi Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse transcriptase
    Jamie Winshell
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    J Biol Chem 279:52924-33. 2004
    ....
  36. ncbi Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level
    Urvi M Parikh
    Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, PA 15261, USA
    J Infect Dis 194:651-60. 2006
    ..Therapy with NRTI combinations that select both pathways simultaneously may delay the emergence of NRTI resistance and prolong treatment response...
  37. ncbi Impact of antigen expression kinetics on the effectiveness of HIV-specific cytotoxic T lymphocytes
    Carel A van Baalen
    Institute of Virology, Erasmus MC Rotterdam, The Netherlands
    Eur J Immunol 32:2644-52. 2002
    ..This provides rationale for immunization strategies that aim at inducing, boosting or skewing CTL responses to early regulatory proteins in AIDS vaccine development...
  38. pmc Mutations proximal to the minor groove-binding track of human immunodeficiency virus type 1 reverse transcriptase differentially affect utilization of RNA versus DNA as template
    Timothy S Fisher
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Virol 77:5837-45. 2003
    ....
  39. ncbi Substitutions at Phe61 in the beta3-beta4 hairpin of HIV-1 reverse transcriptase reveal a role for the Fingers subdomain in strand displacement DNA synthesis
    Timothy S Fisher
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Golding Bldg 401, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    J Mol Biol 325:443-59. 2003
    ..Our results confirm a role for F61 residue in processive synthesis and indicate that the fingers subdomain harbors a structural determinant of strand displacement synthesis by HIV-1 RT...
  40. pmc Cross-clade inhibition of recombinant human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus SIVcpz reverse transcriptases by RNA pseudoknot aptamers
    Daniel M Held
    Department of Molecular Microbiology and Immunology and Department of Biochemistry, University of Missouri School of Medicine, Columbia, Missouri 65211, USA
    J Virol 81:5375-84. 2007
    ..RNA structural diversity therefore translates into a nonoverlapping spectrum of mutations that confer resistance, likely due to differences in atomic-level contacts with RT...
  41. pmc On the importance of the primer activation signal for initiation of tRNA(lys3)-primed reverse transcription of the HIV-1 RNA genome
    Hendrik Huthoff
    Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    Nucleic Acids Res 31:5186-94. 2003
    ..These results reinforce the model of regulated reverse transcription in which the PAS-mediated interaction is critical for efficient initiation...
  42. pmc Does the HIV-1 primer activation signal interact with tRNA3(Lys) during the initiation of reverse transcription?
    Valerie Goldschmidt
    UPR 9002 du CNRS, l Université Louis Pasteur, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Nucleic Acids Res 31:850-9. 2003
    ..Instead, the effects of the vRNA mutations on reverse transcription seem to be linked to incorrect folding of the mutant RNAs...
  43. pmc Structural analyses of purified human immunodeficiency virus type 1 intracellular reverse transcription complexes
    Milan V Nermut
    National Institute of Biological Standards and Control, South Mimms, Potters Bar, Herts EN6 3QG, United Kingdom
    J Virol 77:8196-206. 2003
    ..6 nm thick. Integrase and Vpr are associated with discrete regions of the 6-nm filaments. The nucleic acids within the RTC are coated by small proteins distinct from nucleocapsid and are partially protected from nuclease digestion...
  44. pmc Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors
    Matthew J Gonzales
    Division of Infectious Diseases, Department of Medicine, Stanford University, CA, USA
    AIDS 17:791-9. 2003
    ..To characterize reverse transcriptase (RT) mutations by their association with extent of nucleoside RT inhibitor (NRTI) therapy. To identify mutational clusters in RT sequences from persons receiving multiple NRTI...
  45. pmc The connection domain in reverse transcriptase facilitates the in vivo annealing of tRNALys3 to HIV-1 genomic RNA
    Shan Cen
    Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada
    Retrovirology 1:33. 2004
    ..In this report, we further show that while the RT connection domain in GagPol is not required for tRNALys3 packaging into the virus, it is required for tRNALys3 annealing to the viral RNA genome...
  46. pmc Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations
    Kirsten L White
    Gilead Sciences, Foster City, California, 94404, USA
    Antimicrob Agents Chemother 48:992-1003. 2004
    ..Computer modeling suggests that the increased mobility of the beta3-beta4 loop may contribute to the high-level and broad NRTI resistance caused by the T69 insertion mutation...
  47. pmc Assessment of the role of the central DNA flap in human immunodeficiency virus type 1 replication by using a single-cycle replication system
    Zhujun Ao
    Laboratoire de Rétrovirologie Humaine, Departement de Microbiologie et Immunologie, Faculte de Medecine, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
    J Virol 78:3170-7. 2004
    ..In agreement with previous reports, our data support a functional role of the central DNA flap during the early stages of HIV-1 infection...
  48. pmc Interaction between human immunodeficiency virus type 1 reverse transcriptase and integrase proteins
    Eric A Hehl
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    J Virol 78:5056-67. 2004
    ..Thus, a functional interaction between these two viral enzymes may occur during viral replication...
  49. ncbi Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template binding
    Jason V Cristofaro
    Department of Cell Biology and Molecular Genetics, University of Maryland College Park, Building 231, College Park, Maryland 20742, USA
    Biochemistry 41:10968-75. 2002
    ..In this regard RT is similar to other nucleic acid cleaving enzymes that show enhanced binding upon mutation of active site residues...
  50. ncbi Effects of efavirenz binding on the subunit equilibria of HIV-1 reverse transcriptase
    Carl F Venezia
    Department Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Biochemistry 45:2779-89. 2006
    ..Analysis of crystal structures of the p66/p51 heterodimer reveals that efavirenz binding induces small structural changes at the dimer interface...
  51. ncbi Inhibition of HIV-1 reverse transcription: basic principles of drug action and resistance
    Matthias Gotte
    Jewish General Hospital, McGill University AIDS Center 226, Lady Davis Institute, 3755, chemin Cote Ste Catherine, Montreal, Quebec, Canada H3T 1E2
    Expert Rev Anti Infect Ther 2:707-16. 2004
    ..Focus is placed on biochemical mechanisms and the development of future approaches...
  52. ncbi Substitutions of Phe61 located in the vicinity of template 5'-overhang influence polymerase fidelity and nucleoside analog sensitivity of HIV-1 reverse transcriptase
    Timothy S Fisher
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 277:22345-52. 2002
    ..These results suggest that contacts between the finger subdomain of human immunodeficiency virus type 1 RT and the template 5'-overhang are important determinants of the geometry of the dNTP-binding pocket...
  53. ncbi A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions
    Jerome Deval
    CNRS and Universités d Aix Marseille I et II, UMR 6098, Architecture et Fonction des Macromolecules Biologiques, Ecole Supérieure d Ingénieurs de Luminy Case 925, Marseille, France
    J Biol Chem 279:25489-96. 2004
    ..Processivity of DNA synthesis remains unaffected. These results explain why the two mutations do not combine in the clinic and might give a mechanism for a decreased viral fitness at the molecular level...
  54. ncbi Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis
    Myriam Witvrouw
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Antivir Ther 9:57-65. 2004
    ..Co-receptor antagonists such as AMD3100 show promising anti-HIV-2 therapeutic modalities. Both AMD3100 and enfuvirtide could be used for prophylaxis against SHIV89.6...
  55. ncbi 'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus
    Jason W Rausch
    Reverse Transcriptase Biochemistry Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Building 535, Room 325, Frederick, MD 21702, USA
    Int J Biochem Cell Biol 36:1752-66. 2004
    ..In this review, plus-strand primer processing in HIV-1 is discussed from biochemical, structural, and historical perspectives. A comparative analysis of PPT-processing in different LTR-containing retroelements is also presented...
  56. ncbi Nucleoside and nucleotide analogue reverse transcriptase inhibitors: a clinical review of antiretroviral resistance
    Joel E Gallant
    The Johns Hopkins University, Baltimore, MD, USA
    Antivir Ther 8:489-506. 2003
    ..This review summarizes research advances that further the understanding of nucleoside and nucleotide analogue resistance mutations, and their interplay...
  57. ncbi Characterization of human immunodeficiency virus type 1 Pr160 gag-pol mutants with truncations downstream of the protease domain
    Wei Hao Liao
    Institute of Clinical Medicine, National Yang Ming University School of Medicine, and Department of Medical Research and Education, Taipei Veterans General Hospital, 201 Sec 2 Shih Pai Road, Taipei 11217, Taiwan
    Virology 329:180-8. 2004
    ..This suggests that an intact p51RT domain is required for the Gag-pol to mediate production of mature infectious virus particles in trans...
  58. ncbi Mechanistic insights into the suppression of drug resistance by human immunodeficiency virus type 1 reverse transcriptase using alpha-boranophosphate nucleoside analogs
    Jerome Deval
    CNRS and Universités d Aix Marseille I et II, UMR 6098, Architecture et Fonction des Macromolecules Biologiques, ESIL case 925, 163 Avenue de Luminy, 13288 Marseille Cedex 9, France
    J Biol Chem 280:3838-46. 2005
    ..DNA.dNTP complex and alleviate the requirement of critical amino acids involved in phosphodiester bond formation. To our knowledge, this is the first example of rescue of polymerase activity by means of a nucleotide analog...
  59. ncbi Effects of unpaired nucleotides within HIV-1 genomic secondary structures on pausing and strand transfer
    Christian Lanciault
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 280:2413-23. 2005
    ..Together our data suggest a role for bulge nucleotides in enhancing synthesis through stable secondary structures and reducing strand transfer...
  60. pmc HIV sequence databases
    Carla Kuiken
    Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    AIDS Rev 5:52-61. 2003
    ..The types of data and services these two databases offer, the tools they provide, and the way they are set up and operated are described in detail...
  61. ncbi Efavirenz enhances the proteolytic processing of an HIV-1 pol polyprotein precursor and reverse transcriptase homodimer formation
    Gilda Tachedjian
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, VIC 3004, Australia
    FEBS Lett 579:379-84. 2005
    ..These data suggest that potent mediators of RT dimerization might interfere with the late-stages of viral replication...
  62. ncbi Single-stranded DNA aptamer RT1t49 inhibits RT polymerase and RNase H functions of HIV type 1, HIV type 2, and SIVCPZ RTs
    Jay D Kissel
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    AIDS Res Hum Retroviruses 23:699-708. 2007
    ..This is the first demonstration of universal inhibition of HIV and SIV(cpz) RTs by a nucleic acid aptamer and supports previous reports suggesting that resistance to RT1t49 may be exceptionally infrequent...
  63. ncbi Study of binding stoichiometries of the human immunodeficiency virus type 1 reverse transcriptase by capillary electrophoresis and laser-induced fluorescence polarization using aptamers as probes
    Hao Fu
    Environmental Health Sciences, Department of Public Health Sciences, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Electrophoresis 27:433-41. 2006
    ..This phenomenon was probably a result of fluorescence resonance energy transfer between the two fluorescent molecules bound to the HIV-1 RT protein...
  64. ncbi Mechanistic aspects of HIV-1 reverse transcription initiation
    David Harrich
    HIV Research Unit, Sir Albert Sakzewski Virus Research Centre, Royal Children s Hospital, Herston Road, Herston, Queensland, Australia 4029
    Rev Med Virol 12:31-45. 2002
    ..As viral resistance to many antiretroviral compounds is a continuing problem, understanding the ways in which these factors influence the reverse transcription complex will likely lead to novel antiretroviral strategies...
  65. pmc Intracellular substrates for the primer-unblocking reaction by human immunodeficiency virus type 1 reverse transcriptase: detection and quantitation in extracts from quiescent- and activated-lymphocyte subpopulations
    Anthony J Smith
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, P O Box 016129, Miami, FL 33101 6129, USA
    Antimicrob Agents Chemother 49:1761-9. 2005
    ..While PP(i)-dependent excision may contribute to AZT resistance in vivo, it is likely that selection of AZT-resistant mutants occurs primarily in an environment where the ATP-dependent reaction predominates...
  66. ncbi Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization
    Gilda Tachedjian
    Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, 701 West 168th St, New York, NY 10032, USA
    J Mol Biol 326:381-96. 2003
    ..We conclude that mutations at codons 401 and 414 in p66 impair dimerization by altering the proper positioning of structural elements in between these residues that make important contacts with p51...
  67. ncbi Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a failure to an antiretroviral regimen including tenofovir DF
    Constance Delaugerre
    Department of Virology, Necker Enfants Malades Hospital, 149 rue de Sevres, 75015 Paris, France
    J Clin Virol 32:241-4. 2005
    ..The high selective pressure on the same resistance pathway was probably associated with the loss of antiviral potency, even in well-controlled patient...
  68. pmc K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens
    Peter J Ruane
    Tower ID Medical Associates, Los Angeles, California, USA
    MedGenMed 6:31. 2004
    ....
  69. ncbi Relationship between enzyme activity and dimeric structure of recombinant HIV-1 reverse transcriptase
    G Tachedjian
    Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
    Proteins 60:5-13. 2005
    ..We also propose that the formation of intersubunit interactions in HIV-1 RT regulates the establishment of a functional DNA polymerase active site...
  70. ncbi Antiretroviral efficacy and virological profile of a zidovudine/lamivudine/tenofovir disoproxil fumarate combination therapy in antiretroviral-naive patients
    Bernard Masquelier
    Departement de Virologie et Immunologie biologique, CHU de Bordeaux, France
    Antivir Ther 11:827-30. 2006
    ..To study the antiviral efficacy and the mutations selected by a triple therapy with zidovudine (AZT), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF)...
  71. pmc Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine
    J Gerardo Garcia-Lerma
    HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
    J Virol 78:7545-52. 2004
    ..Our study emphasizes the need for clinical studies to better define the impact of these mutants on treatment responses and evolution of resistance...
  72. ncbi The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes
    David A van de Vijver
    Eijkman Winkler Institute, Department of Virology, University Medical Center Utrecht, G04 614, 3584 CX Utrecht, The Netherlands
    J Acquir Immune Defic Syndr 41:352-60. 2006
    ..This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe...
  73. ncbi Evidence of differential selection of HIV-1 variants carrying drug-resistant mutations in seroconverters
    Stefano Corvasce
    Department of Clinical Sciences Luigi Sacco, Section of Infectious and Tropical Diseases, University of Milan, Milan, Italy
    Antivir Ther 11:329-34. 2006
    ..To estimate the relative efficiency of transmission of different HIV-1 drug-resistance mutations from patients failing treatment, considered as potential transmitters (PTs), to seroconverters (SCs)...
  74. ncbi Temporal characterization of drug resistance associated mutations in HIV-1 protease and reverse transcriptase in patients failing antiretroviral therapy
    Maria Mercedes Santoro
    Department of Experimental Medicine, Tor Vergata University of Rome, Italy
    New Microbiol 29:89-100. 2006
    ....
  75. ncbi Prevalence of HIV-1 drug resistance mutations among Spanish prison inmates
    J García-Guerrero
    Medical Services, Castellón Prison, Crtra de Alcora Km 10, 12071, Castellon, Spain
    Eur J Clin Microbiol Infect Dis 25:695-701. 2006
    ..These findings support the use of resistance testing in HIV-infected inmates who must begin antiretroviral therapy, given the high rate of primary resistance to drugs frequently included in the initial treatment regimens...
  76. ncbi A new strategy based on recombinant viruses as a tool for assessing drug susceptibility of human immunodeficiency virus type 1
    J Garcia-Perez
    AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
    J Med Virol 79:127-37. 2007
    ..In conclusion, the assay permits the quantitation of the level of resistance of clinical HIV-1 isolates to PR and RT inhibitors...
  77. pmc Drug resistance mutations in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase differentially affect the phosphorolysis-dependent primer unblocking activity in the presence of stavudine and zidovudine and its inhib
    Emmanuele Crespan
    IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
    Antimicrob Agents Chemother 49:342-9. 2005
    ..e., drug resistance), the molecular mechanisms underlying this phenotype can be very different. Moreover, the same mutation can give rise to different phenotypes depending on the nature of the substrates and/or inhibitors...
  78. pmc The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions
    Mian er Cong
    Division of HIV AIDS Prevention, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA
    J Virol 81:3037-41. 2007
    ..We conclude that the persistence of transmitted RT mutants might range widely on the basis of fitness and that the modulation of fitness cost by mutational interactions will be a critical determinant of persistence...
  79. pmc HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance
    Robert W Shafer
    Division of Infectious Diseases, Stanford University, Stanford, California, USA
    AIDS 21:215-23. 2007
    ..However, such programs will not produce comparable estimates unless a standardized list of drug-resistance mutations is used to define transmitted resistance...
  80. ncbi Impact of HIV-1 reverse transcriptase polymorphism at codons 211 and 228 on virological response to didanosine
    Anne Genevieve Marcelin
    Department of Virology, Pitie Salpetriere Hospital, Paris, France
    Antivir Ther 11:693-9. 2006
    ..To determine the potential impact of reverse transcriptase (RT) mutations, other than those currently known to confer nucleoside reverse transcriptase inhibitors (NRTIs) resistance, on the virological response to didanosine (ddl)...
  81. ncbi Rare selection of the K65R mutation in antiretroviral-naive patients failing a first-line abacavir/ lamivudine-containing HAART regimen
    Diane Descamps
    Laboratoire de Virologie, Hopital Bichat Claude Bernard, Paris, France
    Antivir Ther 11:701-5. 2006
    ..This study examined whether, in the context of a first-line abacavir/lamivudine highly active antiretroviral therapy (HAART) regimen, K65R might occur as a minority population where L74V was detected at virological failure...
  82. ncbi The epidemiology of antiretroviral drug resistance among drug-naive HIV-1-infected persons in 10 US cities
    Hillard S Weinstock
    Division of HIV AIDS Prevention, Surveillance and Epidemiology, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
    J Infect Dis 189:2174-80. 2004
    ..The prevalence and characteristics of persons with newly diagnosed human immunodeficiency virus (HIV) infections with or without evidence of mutations associated with drug resistance have not been well described...
  83. ncbi In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in Human Immunodeficiency Virus-infected patients
    Nicola Gianotti
    Clinic of Infectious Diseases, Vita Salute San Raffaele University, Milan, Italy
    New Microbiol 28:319-26. 2005
    ..This suggests that the K103N mutation per se has little impact on viral fitness in vivo...
  84. ncbi Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients
    Atsuko Hachiya
    AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan
    Virology 327:215-24. 2004
    ..Our study identified a novel NVP resistance-associated mutation, K238S, which could be persistently detected by genotypic assay longer than V106A and V108I during off-treatment period...
  85. ncbi Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: a randomized placebo-controlled trial
    Jean Michel Molina
    Department of Infectious Diseases, Saint Louis Hospital, Paris, France
    J Infect Dis 191:840-7. 2005
    ..The antiviral efficacy of didanosine in patients experiencing virological failure is not well known...
  86. ncbi [Prevalence of drug resistance mutations among antiretroviral drug-naive HIV-1-infected patients in China]
    Xue feng Si
    National Center for AIDS STD Prevention and Control, China Center for Disease Prevention and Control, Beijing 100050, China
    Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 18:308-11. 2004
    ..To collect background information on drug-resistant HIV-1 strains in various regions before the start of nation-wide antiretroviral therapy in China...
  87. ncbi Analysis of discrepancies in the interpretation of antiretroviral drug resistance results in HIV-1 infected patients of Basque Country, Spain
    MERCEDES MUNOZ
    Viral Pathogenesis Department, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera de Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain
    J Clin Virol 33:224-9. 2005
    ..However, some levels of discordance among them has been described...
  88. ncbi Long-term analysis of the resistance development in HIV-1 positive patients treated with protease and reverse transcriptase inhibitors: correlation of the genotype and disease progression
    J Vaclavikova
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam 2, 166 10 Prague, Czech Republic
    Acta Virol 49:29-36. 2005
    ..Efficient yet temporary suppression of viral replication was achieved by a lopinavir (LPV) treatment...
  89. ncbi Accuracy, precision, and consistency of expert HIV type 1 genotype interpretation: an international comparison (The GUESS Study)
    Andrew R Zolopa
    Stanford University School of Medicine, Stanford, CA 94305 5107, USA
    Clin Infect Dis 41:92-9. 2005
    ..We sought to determine how much agreement exists within a group of experts in the interpretation of complex genotypes...
  90. ncbi Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after single-dose nevirapine
    Dana Jones
    Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
    AIDS Res Hum Retroviruses 21:319-24. 2005
    ..Further studies are needed to evaluate whether selection of minority variants with one or more NVPR mutations after single-dose NVP is clinically relevant...
  91. pmc The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations
    Luis R Miranda
    Section of Retroviral Therapeutics, Brigham and Women s Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts, USA
    Antimicrob Agents Chemother 49:2648-56. 2005
    ....
  92. ncbi Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece
    D Paraskevis
    Department of Hygiene and Epidemiology, Athens University Medical School, Mikras Asias 75, GR 11527 Athens, Greece
    Virus Res 112:115-22. 2005
    ..For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%...
  93. ncbi Analysis of drug resistance-associated mutations in treatment-naïve individuals infected with different genetic forms of HIV-1 circulating in countries of the former Soviet Union
    E Vazquez de Parga
    Instituto de Salud Carlos III, Madrid, Spain
    J Med Virol 77:337-44. 2005
    ..These data underline the importance of genotypic resistance testing of chronically HIV-1-infected patients before initiating treatment, in order to select the most suitable drug regimen...
  94. ncbi Drug-resistance mutations in antiretroviral-naïve patients with established HIV-1 infection in Mexico
    M Escoto-Delgadillo
    Laboratory of Immunodeficiencies and Human Retrovirus, Western Biomedical Research Center, Mexican Institute of Social Security, Guadalajara, Mexico
    HIV Med 6:403-9. 2005
    ..To describe the prevalence of baseline drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naïve patients from Mexico with established HIV-1 infection...
  95. ncbi Long-term persistence of primary genotypic resistance after HIV-1 seroconversion
    David Pao
    Royal Sussex County Hospital, Brighton, United Kingdom
    J Acquir Immune Defic Syndr 37:1570-3. 2004
    ....
  96. ncbi HIV type 1 BF recombinant strains exhibit different pol gene mosaic patterns: descriptive analysis from 284 patients under treatment failure
    Jorge F Quarleri
    Centro Nacional de Referencia para el SIDA, Departamento de Microbiologia, Facultad de Medicina, Universidad de Buenos Aires, 1121 Buenos Aires, Argentina
    AIDS Res Hum Retroviruses 20:1100-7. 2004
    ..No association was observed between the prevalence of each mosaic pattern and the frequency of major drug-resistance mutations in PR and RT...
  97. ncbi Prevalence of drug resistance and newly recognised treatment-related substitutions in the HIV-1 reverse transcriptase and protease genes from HIV-positive patients naïve for anti-retrovirals
    C Torti
    Institute of Infectious and Tropical Diseases, University of Brescia, 25123 Brescia, Italy
    Clin Microbiol Infect 10:826-30. 2004
    ..These findings support the use of resistance testing in patients naïve for anti-retroviral therapy, and suggest that the possible impact of newly recognised treatment-related mutations on clinical outcome requires further investigation...
  98. ncbi Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA
    M R Jakobsen
    Department of Infectious Diseases, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardvej 100, 8200 Aarhus N, Denmark
    J Clin Virol 39:215-21. 2007
    ..Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment...
  99. ncbi Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries
    Laurence Vergne
    University of Montpellier I, Montpellier, France
    J Acquir Immune Defic Syndr 29:165-8. 2002
    ..A continuous surveillance of the circulation of ARV drug-resistant viruses must be organized to guide ARV treatment strategies and policies...
  100. ncbi How does expert advice impact genotypic resistance testing in clinical practice?
    Sheila M Badri
    Division of Infectious Diseases, John H Stroger, Jr Hospital of Cook County, Chicago, IL 60612, USA
    Clin Infect Dis 37:708-13. 2003
    ..01). Consideration should be given to enlisting expert assistance in the interpretation of GRT results in routine clinical practice...
  101. ncbi Indinavir plasma concentrations and resistance mutations in patients experiencing early virological failure
    Daniel Gonzalez de Requena
    Pharmacology Unit, Hospital Carlos III, Instituto de Salud Carlos III, 28035 Madrid, Spain
    AIDS Res Hum Retroviruses 19:457-9. 2003
    ..Thus, drug monitoring may be useful to assess treatment adherence and risk of drug resistance in early virological failures. This information may be crucial for choosing the most appropriate rescue intervention...

Research Grants62

  1. Primate Model Towards HIV Eradication Strategies
    RAYMOND FELIX SCHINAZI; Fiscal Year: 2012
    ..The success of such induction strategies will likely be dependent on the ability of fully suppressive HAART to prevent replication of reactivated virus. ..
  2. Determinants of HIV Dynamics and Variation
    JOSE ORLANDO MALDONADO-ORTIZ; Fiscal Year: 2013
    ....
  3. Discovery of Novel HIV-1 Reverse Transcriptase Inhibitors by Fragment Screening
    ANGELA MCKOY; Fiscal Year: 2013
    ..The fragment screening approach allows for efficient search of chemical space and should lead to the identification of novel scaffolds for inhibiting HIV-1 RNH activity at both the active site and allosteric pockets. ..
  4. Novel mechanisms of HIV resistance to RTIs
    NICOLAS P SLUIS-CREMER; Fiscal Year: 2012
    ....
  5. Rational Design of NRTI for Drug Resistant HIV-1
    John W Mellors; Fiscal Year: 2010
    ..The identification and development of the novel ADPs through the rational design and assessments proposed in this application could help meet the expanding need for potent and safe NRTI that are active against drug-resistant HIV-1. ..
  6. Inhibitors of host kinases as molecular targets for immune defense against HIV-1
    Mathias Lichterfeld; Fiscal Year: 2013
    ....
  7. Molecular Recognition of Proteins and Ligand Design
    William L Jorgensen; Fiscal Year: 2013
    ..Though much work remains to be done to find optimal inhibitors of HIV replication and regulators of MIF signaling, Tdp1 is a promising new target for cancer chemotherapy that is also under investigation. ..
  8. Mechanism and Regulation of HIV-1 Uncoating
    CHRISTOPHER R AIKEN; Fiscal Year: 2013
    ..Aim 5. Identification of novel capsid-interacting host factors. These studies will answer fundamental question in retrovirus biology and will clarify the mechanisms of restriction by endogenous host cell factors. ..
  9. Structual studies of HIV-1 integration
    Mamuka Kvaratskhelia; Fiscal Year: 2013
    ..The obtained results will improve our understanding of how this key retroviral enzyme functions and contribute to wider efforts in the field focused on discovery of new antiretroviral therapies. 1 ..
  10. HIV-1 reverse transcriptase structure: function, inhibition, and resistance
    EDWARD V ARNOLD; Fiscal Year: 2013
    ..The proposed studies will enhance opportunities for targeting known and new sites on RT including RNase H, the only HIV enzyme not yet blocked by anti-AIDS drugs. ..
  11. Computer-Aided Design of Anti-HIV Drugs
    William L Jorgensen; Fiscal Year: 2013
    ..Similar analyses are being carried out for the other prominent clinical variant, Lys103Asn;only a ca. 10-fold gain is needed to bring the potency towards strains with this replacement to the 10-nM level. ..
  12. Subunit Assembly and Substrate Interactions in HIV-1 RT
    MARY BARKLEY; Fiscal Year: 2009
    ..Characterize inhibitor binding to RT. 2. Determine inhibitor effects on individual steps in DMA polymerization. 3. Investigate inhibitor effects on conformation and dynamics of RT subunits and assembly. ..
  13. Predictive QSAR Modeling of HIV-1 Integrase Inhibitors
    Rajni Garg; Fiscal Year: 2009
    ..The goal of this project is to understand the interactions between the HIV-1 integrase enzyme and its inhibitors that will help in the design of new drugs active against drug-resistant HIV-1. ..
  14. The Enzymology of M-MuLV and HIV Replication
    JAMES CHAMPOUX; Fiscal Year: 2009
    ..The analysis of reverse transcriptase fidelity during displacement synthesis will directly contribute to our understanding of how the virus rapidly evolves during progression to AIDS. ..
  15. MOLECULAR RECOGNITION OF HIV1 PRIMER TRNA LYS
    Karin Musier Forsyth; Fiscal Year: 2001
    ..c) Stopped-flow fluorescence techniques will be used to investigate the kinetic mechanism of NC unwinding and annealing of tRNALys,3. ..
  16. Synthesis of New NNRTLs for the Treatment of AIDS
    Mark Cushman; Fiscal Year: 2005
    ..The activities of the ADAMs vs. NNRTI resistant viruses will be investigated. The aqueous solubilities of the new ADAMs will be measured accurately. ..
  17. SV40-BASED COMBINATION GENETIC THERAPIES FOR HIV/SIV
    David Strayer; Fiscal Year: 2003
    ..abstract_text> ..
  18. LENTIVIRUS ATTENUATION THROUGH HIGH FIDELITY REPLICATION
    Stephen Dewhurst; Fiscal Year: 2002
    ..These experiments are expected to provide insight as to the potential utility of using high fidelity RT mutants to improve the safety of live-attenuated HIV vaccines. ..
  19. SUSTAINED HIV1 SUPPRESSION DESPITE DRUG RESISTANCE
    Victoria Johnson; Fiscal Year: 2000
    ..It is expected that the understanding of the mechanism(s) that contribute to sustained HIV-1 suppression may allow definition of more rationale therapeutic strategies for treatment of HIV-1 individuals. ..
  20. NUCLEOSIDES WITH DUAL ANTIHIV AND HBV ACTIVITY
    RAYMOND SCHINAZI; Fiscal Year: 1999
    ..Radiolabeled D-D4FC and L-D4FC will be synthesized and their cellular pharmacology will be determined in order to gain insight into their different biological properties. ..
  21. COMBINATORIAL & RATIONAL DESIGN APTAMERS TARGETING HIV
    David Gorenstein; Fiscal Year: 2004
    ..abstract_text> ..
  22. ENZYMOLOGY OF M-MULV AND HIV REPLICATION
    JAMES CHAMPOUX; Fiscal Year: 1999
    ..Experiments will be undertaken to isolate and characterize mutants that are defective in helix unwinding as a means to identify the domains of the reverse transcriptases responsible for displacement synthesis. ..
  23. Mechanics and Mechanisms of HIV Reverse Transcriptase
    David Keller; Fiscal Year: 2003
    ..6. Use the data gathered from the single-molecule studies, together with structural data from X-ray crystallography and data from ensemble kinetic measurements, to build and test a detailed structural and mechanical model for WV RI. ..
  24. Novel Inhibitors of HIV-1 Reverse Transcriptase
    BRYAN O HARA; Fiscal Year: 2003
    ..S. If the drug developed has a new mechanism of action, this would further expand the appropriate patient population. ..
  25. Synthesis of Nucleoside Analogs as HIV-1 Reverse Transcriptase Inhibitors
    KIMBERLYNN DAVIS; Fiscal Year: 2007
    ..This research focuses on the design and synthesis of novel NRTIs to more effectively treat the virus and prevent progression to full-blown AIDS. [unreadable] [unreadable] [unreadable]..
  26. Rational, Computational Design of Novel anti-AIDS Drugs
    Richard Smith; Fiscal Year: 2003
    ....
  27. KEY INTERACTIONS FOR HIV 1 RT STABILITY AND DIMERIZATION
    Andrew Kaplan; Fiscal Year: 2005
    ..These RTs will be cloned in our expression system to allow direct study of conserved critical interactions. ..
  28. Alkylglycero-PFA Analogs for Treating Drug Resistant HIV
    Kevin Anderson; Fiscal Year: 2005
    ..abstract_text> ..
  29. TWO-SITE INHIBITORS FOR HIV RT: EXTREMELY TIGHT BINDERS?
    KATHLYN PARKER; Fiscal Year: 2001
    ..to modify the structures of lead compounds, if necessary, in order to minimize the appearance of resistant strains. ..
  30. FIDELITY AND DYNAMICS OF DNA SYNTHESIS
    JAMES PELISKA; Fiscal Year: 2001
    ..abstract_text> ..
  31. BIOCHEMICAL EVALUATION OF RT-TEMPLATE-PRIMER/COMPLEXES
    MARY BARKLEY; Fiscal Year: 2001
    ....
  32. STRUCTURE, MECHANISM AND INHIBITION OF HIV PROTEINS
    Stephen Harrison; Fiscal Year: 2002
    ..Another goal is to determine whether interacting surfaces on these cellular proteins might provide suitably specific targets for screening ligands. ..
  33. Inhibitors of the HIV-1 preintegration complex
    MICHAEL HARPOLD; Fiscal Year: 2003
    ..When these studies are complete, it should be possible to begin developing drugs that block HIV-1 replication by inhibiting the PIC. Such drugs could become a new modality for treating HIV infection. ..
  34. An AIDS Vaccine Strategy uding hCCR5-lgG Fusion Proteins
    Quan Zhu; Fiscal Year: 2005
    ..Data generated herein will provide valuable information not only for design of an AIDS vaccine but also for general vaccine strategy targeting self-antigen, thus warrants further NIH R01 funding. ..
  35. NOVEL ASSAY FOR MEASURING THE INHIBITION OF HIV-1 ENTRY
    Christos Petropoulos; Fiscal Year: 2002
    ..The assay will be marketed to physicians to assist in HIV/AIDS patient care, as well as pharmaceutical companies to support their drug and vaccine development programs. ..
  36. Impact of efavirenz resistance mutations on HIV-1
    Christine Koval; Fiscal Year: 2006
    ..abstract_text> ..
  37. MECHANISMS OF HIV1 VARIATION
    LOUIS MANSKY; Fiscal Year: 2001
    ..Combinations will also include NC proteins, if variants are characterized that influence the mutation rate. ..
  38. Development of a UC-781 Combination Microbicide
    Joseph Romano; Fiscal Year: 2002
    ..abstract_text> ..
  39. RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY
    THOMAS NORTH; Fiscal Year: 2000
    ..Long-term goals are utilize the model to probe sites of virus replication and/or persistence in prolonged HAART, and to evaluate other intervention approaches in attempts to eradicate virus from reservoirs. ..
  40. Computational Prediction of Biomolecular Dynamics
    Ivet Bahar; Fiscal Year: 2007
    ..This novel computational methodology will fill a unique niche due to its applicability to large structures and assemblies, its speed and accessibility to the scientific community. ..
  41. ROBOTIC SYSTEM FOR TIME-RESOLVED FUNCTIONAL TOPOGRAPHY
    ALEX KOGON; Fiscal Year: 2005
    ..The system will be broadly applicable to functional topography studies of a variety of macromolecular complexes that are crucial for our understanding of cancer and other diseases. ..
  42. PHI-443: Novel Non-Spermicidal Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of PHI-443 in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  43. NOVEL CONTRACEPTIVES WITH ANTI-HIV ACTIVITY
    OSMOND D CRUZ; Fiscal Year: 2001
    ..The preclinical data on in vivo efficacies of WHI-05 and WHI-07 will be essential to further explore the utility of these novel drugs for clinical studies in human patients. ..
  44. Stampidine: A Novel Broad-Spectrum Anti-HIV Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ..Specific Aims 1 and 2 may provide the foundation for the clinical development of STAMP in Phase II studies as a safe, effective broad-spectrum anti-HIV microbicide without conception-inhibiting functions. ..
  45. Drug Resistance in Non-Subtype B HIV-1
    Susan Eshleman; Fiscal Year: 2005
    ..abstract_text> ..
  46. FLP-102: Rationally Engineered Antiviral Protein
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The preclinical data on FLP-102 will be essential to further explore the utility of this novel recombinant PAP mutant for Phase II. ..
  47. PHI 346: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2003
    ..Following successful completion of the Phase I in vivo efficacy studies, gel formulation of PHI-346 will be further explored as a vaginal dual-function microbicide in Phase II. ..
  48. Phase II SBIR: WHI-07: A Novel Dual-Function Microbicide
    OSMOND D CRUZ; Fiscal Year: 2005
    ....
  49. Vanadocenes as a New Class of Spermicidal Drugs
    OSMOND D CRUZ; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. METVAN: A Novel Anticancer Agent
    OSMOND D CRUZ; Fiscal Year: 2003
    ..The knowledge gained from these studies described under Specific Aims 1-2 is expected to facilitate the design of innovative treatment regimens employing METVAN for metastatic breast cancer and brain tumor patients. ..
  51. Universal Technology for Profiling the Dynamics of Normal & Oncogenic Signaling
    Karen Anderson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  52. A Molecular Approach For Opportunistic HIV-1 Infections
    Karen Anderson; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  53. DELETION MUTAGENESIS WITHIN NONCODING SEGMENTS OF HIV1
    Mark Wainberg; Fiscal Year: 2001
    ..6. To determine whether these attenuated SIV constructs may protect against subsequent challenge with virulent forms of SIV and SIV/HIV hybrids. ..
  54. ROLE OF MULTIDRUG RESISTANCE MUTATION IN HIV FITNESS
    Prem Sharma; Fiscal Year: 2002
    ....
  55. MECHANISTIC STUDIES ON PEP UTILIZING ENZYMES
    Karen Anderson; Fiscal Year: 2003
    ..In addition as the investigator develops the quantitative aspects of the rapid mixing, pulsed-flow ESI-MS technique further, she will extend the studies of these enzymes to determine the full kinetic profile. ..
  56. Novel Approach to Study Transient Enzyme Intermediates
    Karen Anderson; Fiscal Year: 2008
    ..These studies will aid in pioneering a powerful and novel analytical methodology for detecting, characterizing and quantitating enzyme intermediates on a rapid time scale. ..
  57. RT-SHIV MODEL FOR RESISTANCE TO AIDS THERAPY
    THOMAS NORTH; Fiscal Year: 2002
    ..Long-term goals are (to) utilize the model to probe sites of virus replication and/or persistence in prolonged HAART, and to evaluate other intervention approaches in attempts to eradicate virus from reservoirs. ..
  58. SIV MODEL FOR MULTIDRUG RESISTANCE TO AIDS THERAPY
    THOMAS NORTH; Fiscal Year: 2002
    ..In addition, they will also evaluate efficacy of combination treatment of 3TC/PMPA, or the triple combination of AZT/3TC/PMPA, and will characterize any resistant mutants that arise following these treatments. ..
  59. HIV-1 RT dimerization as an antiviral target
    Nicolas Sluis Cremer; Fiscal Year: 2005
    ..abstract_text> ..
  60. Public HIV Drug Resistance Database
    ROBERT WILLIAM SHAFER; Fiscal Year: 2010
    ..UCL is on the forefront of research into the problem of transmitted drug resistance and Oxford University is on the forefront of research on virus evolution and population genetics. ..
  61. A Monkey Model for Anti-Cytomegalovirus Therapy
    THOMAS NORTH; Fiscal Year: 2006
    ..Ultimately, we predict that this model can be used to test therapies for CMV infections during AIDS, Transplantation, or fetal development in a primate host that can be experimentally manipulated. ..