virus integration

Summary

Summary: Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA; (LYSOGENY); to form a PROPHAGE or integration of retroviral DNA into cellular DNA to form a PROVIRUS.

Top Publications

  1. ncbi Identification of host proteins required for HIV infection through a functional genomic screen
    Abraham L Brass
    Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 319:921-6. 2008
  2. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
  3. pmc BET proteins promote efficient murine leukemia virus integration at transcription start sites
    Amit Sharma
    Center for Retrovirus Research, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 110:12036-41. 2013
  4. ncbi A quantitative assay for HIV DNA integration in vivo
    S L Butler
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA
    Nat Med 7:631-4. 2001
  5. ncbi A role for LEDGF/p75 in targeting HIV DNA integration
    Angela Ciuffi
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104 6076, USA
    Nat Med 11:1287-9. 2005
  6. pmc Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization
    Frauke Christ
    Katholieke Universiteit Leuven, Molecular Virology and Gene Therapy VCTB 5, Leuven, Belgium
    Antimicrob Agents Chemother 56:4365-74. 2012
  7. pmc New class of HIV-1 integrase (IN) inhibitors with a dual mode of action
    Manuel Tsiang
    Gilead Sciences, Inc, Foster City, California 94404, USA
    J Biol Chem 287:21189-203. 2012
  8. pmc HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
    Gary P Wang
    University of Pennsylvania, School of Medicine, Department of Microbiology, Philadelphia, PA 19104 6076, USA
    Genome Res 17:1186-94. 2007
  9. pmc The mechanism of retroviral integration from X-ray structures of its key intermediates
    Goedele N Maertens
    Division of Infectious Diseases, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 468:326-9. 2010
  10. pmc Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration
    Jean L Mbisa
    HIV Drug Resistance Program, SAIC Frederick, Inc, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    J Virol 81:7099-110. 2007

Detail Information

Publications321 found, 100 shown here

  1. ncbi Identification of host proteins required for HIV infection through a functional genomic screen
    Abraham L Brass
    Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 319:921-6. 2008
    ..This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing identify potential targets for therapy...
  2. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
    ..Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter...
  3. pmc BET proteins promote efficient murine leukemia virus integration at transcription start sites
    Amit Sharma
    Center for Retrovirus Research, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 110:12036-41. 2013
    ..These findings elucidate the importance of BET proteins for MLV integration efficiency and targeting and provide a route to developing safer MLV-based vectors for human gene therapy. ..
  4. ncbi A quantitative assay for HIV DNA integration in vivo
    S L Butler
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA
    Nat Med 7:631-4. 2001
    ..The integration assay employs a novel quantitative form of Alu-PCR that should be generally applicable to studies of integrating viruses and gene transfer vectors...
  5. ncbi A role for LEDGF/p75 in targeting HIV DNA integration
    Angela Ciuffi
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, Pennsylvania 19104 6076, USA
    Nat Med 11:1287-9. 2005
    ..LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells...
  6. pmc Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization
    Frauke Christ
    Katholieke Universiteit Leuven, Molecular Virology and Gene Therapy VCTB 5, Leuven, Belgium
    Antimicrob Agents Chemother 56:4365-74. 2012
    ..The allosteric nature of inhibition and compatibility with INSTIs underline an interest in further (clinical) development of LEDGINs...
  7. pmc New class of HIV-1 integrase (IN) inhibitors with a dual mode of action
    Manuel Tsiang
    Gilead Sciences, Inc, Foster City, California 94404, USA
    J Biol Chem 287:21189-203. 2012
    ..For the first time, tBPQAs were demonstrated to be allosteric inhibitors of HIV-1 IN displaying a dual mode of action: inhibition of IN-viral DNA assembly and inhibition of IN-LEDGF interaction...
  8. pmc HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications
    Gary P Wang
    University of Pennsylvania, School of Medicine, Department of Microbiology, Philadelphia, PA 19104 6076, USA
    Genome Res 17:1186-94. 2007
    ..The pyrosequencing and bioinformatic methods described here should be useful for investigating many aspects of retroviral DNA integration...
  9. pmc The mechanism of retroviral integration from X-ray structures of its key intermediates
    Goedele N Maertens
    Division of Infectious Diseases, Imperial College London, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Nature 468:326-9. 2010
    ..Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences...
  10. pmc Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration
    Jean L Mbisa
    HIV Drug Resistance Program, SAIC Frederick, Inc, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    J Virol 81:7099-110. 2007
    ..These novel observations suggest that HIV-1 cDNA produced in the presence of A3G exhibits defects in primer tRNA processing, plus-strand DNA transfer, and integration...
  11. pmc TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core
    José Carlos Valle-Casuso
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA
    J Virol 86:5931-6. 2012
    ..Overall, this work suggests that TNPO3 interacts with the incoming HIV-1 core in the cytoplasm to assist a process that is important for HIV-1 infection after nuclear import...
  12. pmc The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients
    Zhaoshi Jiang
    Department of Bioinformatics and Computational Biology, Genentech Inc, South San Francisco, California 94080, USA
    Genome Res 22:593-601. 2012
    ..Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals...
  13. pmc Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model
    Liang Shan
    Department of Medicine, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
    J Virol 85:5384-93. 2011
    ..Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4(+) T cells...
  14. pmc Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies
    Laurence Colin
    Institut de Biologie et de Médecine Moléculaires IBMM, Universite Libre de Bruxelles ULB, Gosselies, Belgium
    Retrovirology 6:111. 2009
    ..While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway...
  15. pmc Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes
    Yefei Han
    Department of Medicine, Ross 1049, School of Medicine, Johns Hopkins University, 720 Rutland Ave, Baltimore, MD 21205, USA
    J Virol 78:6122-33. 2004
    ..Taken together, these results demonstrate that HIV-1 genomes reside within actively transcribed host genes in resting CD4+ T cells in vivo...
  16. ncbi Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication
    Frauke Christ
    Laboratory for Molecular Virology and Gene Therapy, Division of Molecular Medicine, Katholieke Universiteit Leuven KULeuven, Leuven, Belgium
    Nat Chem Biol 6:442-8. 2010
    ..Our work demonstrates the feasibility of rational design of small molecules inhibiting the protein-protein interaction between a viral protein and a cellular host factor...
  17. pmc 3'-processing and strand transfer catalysed by retroviral integrase in crystallo
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London, UK
    EMBO J 31:3020-8. 2012
    ..The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules...
  18. pmc Endogenous non-retroviral RNA virus elements in mammalian genomes
    Masayuki Horie
    Department of Virology, Research Institute for Microbial Diseases BIKEN, Osaka University, Osaka 565 0871, Japan
    Nature 463:84-7. 2010
    ....
  19. pmc Bromo- and extraterminal domain chromatin regulators serve as cofactors for murine leukemia virus integration
    Saumya Shree Gupta
    Institute of Virology, Hannover Medical School, Hannover, Germany
    J Virol 87:12721-36. 2013
    ..Our data suggest that BET proteins might act as chromatin-bound acceptors for the MLV preintegration complex. These results could pave a way to redirecting MLV DNA integration as a basis for creating safer retroviral vectors. ..
  20. ncbi Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions
    Nicolas Wentzensen
    Division of Molecular Pathology, Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
    Oncogene 21:419-26. 2002
    ..These data demonstrate that target directed insertional mutagenesis might occur in few HPV-induced anogenital lesions, however, it is rather the exception than the rule...
  21. pmc Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration
    Lihong Zhou
    Wohl Virion Centre, Division of Infection and Immunity, University College London, London, United Kingdom
    PLoS Pathog 7:e1002194. 2011
    ..The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells...
  22. pmc Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection
    Theodore C Pierson
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Virol 76:8518-31. 2002
    ..Our results demonstrate that the preintegration state is labile and decays rapidly (half-life = 1 day) following the entry of HIV-1 into a resting T cell, with significant decay occurring during the slow process of reverse transcription...
  23. ncbi Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression
    Jonah B Sacha
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Immunol 178:2746-54. 2007
    ..0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag...
  24. pmc Selection of target sites for mobile DNA integration in the human genome
    Charles Berry
    Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS Comput Biol 2:e157. 2006
    ....
  25. pmc The BET family of proteins targets moloney murine leukemia virus integration near transcription start sites
    Jan De Rijck
    Laboratory for Molecular Virology and Gene Therapy, KU Leuven, 3000 Leuven, Belgium
    Cell Rep 5:886-94. 2013
    ..Together, these data validate BET proteins as MLV integration targeting factors...
  26. pmc VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue
    Yunxin Chen
    Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Bioinformatics 29:266-7. 2013
    ..Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity. VirusSeq can also perform this function using whole-genome sequencing data of human tissue...
  27. ncbi Effective gene therapy with nonintegrating lentiviral vectors
    Rafael J Yáñez-Muñoz
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Med 12:348-53. 2006
    ..For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis...
  28. ncbi HIV-1 integration in the human genome favors active genes and local hotspots
    Astrid R W Schroder
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 110:521-9. 2002
    ..4 kb region containing 1% of sites. These data document unexpectedly strong biases in integration site selection and suggest how selective targeting promotes aggressive HIV replication...
  29. pmc Elite suppressors harbor low levels of integrated HIV DNA and high levels of 2-LTR circular HIV DNA compared to HIV+ patients on and off HAART
    Erin H Graf
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS Pathog 7:e1001300. 2011
    ..Moreover, they add significantly to our understanding of the mechanisms that allow viral control and reservoir maintenance in this unique patient population...
  30. ncbi HIV-1 proviral DNA excision using an evolved recombinase
    Indrani Sarkar
    Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D 01307 Dresden, Germany
    Science 316:1912-5. 2007
    ..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...
  31. pmc The role of unintegrated DNA in HIV infection
    Richard D Sloan
    McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada
    Retrovirology 8:52. 2011
    ..This review focuses on the role of unintegrated DNA in HIV infection and additionally considers the potential implications for antiviral therapy...
  32. pmc Retroviral DNA integration: viral and cellular determinants of target-site selection
    Mary K Lewinski
    Infectious Disease Laboratory, The Salk Institute, La Jolla, California, USA
    PLoS Pathog 2:e60. 2006
    ....
  33. pmc The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro
    Jesse H Arbuckle
    Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA
    Proc Natl Acad Sci U S A 107:5563-8. 2010
    ....
  34. pmc Foamy virus vector integration sites in normal human cells
    Grant D Trobridge
    Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:1498-503. 2006
    ..Transcriptional profiling showed that gene expression had little influence on integration site selection. Our findings suggest that FV vectors may have desirable integration properties for gene therapy applications...
  35. pmc Revisiting HIV-1 uncoating
    Nathalie Arhel
    Department of Virology, URA3015, Institut Pasteur, 25 28 rue du Dr, Roux, 75015 Paris, France
    Retrovirology 7:96. 2010
    ....
  36. ncbi HIV-1 integrase forms stable tetramers and associates with LEDGF/p75 protein in human cells
    Peter Cherepanov
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    J Biol Chem 278:372-81. 2003
    ....
  37. pmc HIV DNA integration
    Robert Craigie
    Molecular Virology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USA
    Cold Spring Harb Perspect Med 2:a006890. 2012
    ..Models for some of the molecular mechanisms involved have been proposed, but important details remain to be clarified...
  38. pmc Virus-producing cells determine the host protein profiles of HIV-1 virion cores
    Steven Santos
    Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, 2300 I Street NW, Ross Hall, Washington, DC 20037, USA
    Retrovirology 9:65. 2012
    ..However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized...
  39. pmc Analysis of early human immunodeficiency virus type 1 DNA synthesis by use of a new sensitive assay for quantifying integrated provirus
    Audrey Brussel
    Departement des Maladies Infectieuses, Institut Cochin, INSERM U567, CNRS UMR 8104, Universite Rene Descartes, 22 rue Mechain, 75014 Paris, France
    J Virol 77:10119-24. 2003
    ..Parallel assays for total HIV-1 DNA and two-LTR HIV-1 DNA circles allowed the synthesis and fate of the different HIV-1 DNA species to be monitored upon a single round of viral replication...
  40. pmc Viral DNA tethering domains complement replication-defective mutations in the p12 protein of MuLV Gag
    William M Schneider
    Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
    Proc Natl Acad Sci U S A 110:9487-92. 2013
    ..Analysis of the integration-site selection of these chimeric viruses showed no significant change in integration profile compared with wild-type MuLV, suggesting release of the tethered p12 post mitosis, before viral integration...
  41. ncbi High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors
    Claudia Cattoglio
    Istituto Scientifico H San Raffaele, Milan, Italy
    Blood 116:5507-17. 2010
    ....
  42. pmc Kinetics of human immunodeficiency virus type 1 decay following entry into resting CD4+ T cells
    Yan Zhou
    Johns Hopkins University School of Medicine, 720 Rutland Ave, Baltimore, MD 21205, USA
    J Virol 79:2199-210. 2005
    ..Therefore, the reservoir of unintegrated HIV-1 in recently infected resting CD4(+) T cells is highly labile...
  43. pmc The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones
    Nicolas A Gillet
    Department of Immunology, Wright Fleming Institute, Imperial College London, London, UK
    Blood 117:3113-22. 2011
    ..The abundance of established HTLV-1 clones is determined by genomic features of the host DNA flanking the provirus. HTLV-1 clonal expansion in vivo is favored by orientation of the provirus in the same sense as the nearest host gene...
  44. pmc Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration
    Andrea L Ferris
    HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 107:3135-40. 2010
    ..The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy...
  45. pmc Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough
    Yefei Han
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell Host Microbe 4:134-46. 2008
    ..Due to the nature of HIV-1 integration sites in vivo, this orientation-dependent regulation can influence the vast majority of infected cells and adds complexity to the maintenance of latency...
  46. ncbi Transcription start regions in the human genome are favored targets for MLV integration
    Xiaolin Wu
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 8004, USA
    Science 300:1749-51. 2003
    ..Defining different integration site preferences for retroviruses will have important ramifications for gene therapy and may aid in our understanding of the factors directing the integration process...
  47. pmc The SET complex acts as a barrier to autointegration of HIV-1
    Nan Yan
    Department of Pediatrics, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Pathog 5:e1000327. 2009
    ..Therefore, the SET complex facilitates HIV-1 infection by preventing suicidal autointegration...
  48. pmc Detecting HIV-1 integration by repetitive-sampling Alu-gag PCR
    Megan K Liszewski
    Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Pennsylvania, 3620 Hamilton Walk, 265 JMB, Philadelphia, PA 19104, USA
    Methods 47:254-60. 2009
    ..Finally, we speculate on fundamental, unresolved issues in HIV latency that can be addressed by measuring HIV integration...
  49. pmc Weak palindromic consensus sequences are a common feature found at the integration target sites of many retroviruses
    Xiaolin Wu
    Laboratory of Molecular Technology, Scientific Application International Corporation, National Cancer Institute at Frederick, 915 Toll House Ave, Frederick, MD 21701, USA
    J Virol 79:5211-4. 2005
    ....
  50. ncbi The majority of viral-cellular fusion transcripts in cervical carcinomas cotranscribe cellular sequences of known or predicted genes
    Irene Kraus
    Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway
    Cancer Res 68:2514-22. 2008
    ..These data suggest that the influence of HPV integration on host gene expression may not be a rare effect and should encourage more detailed analyses...
  51. ncbi A role for DNA-PK in retroviral DNA integration
    R Daniel
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Science 284:644-7. 1999
    ..These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway...
  52. pmc Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique
    Panu Peitsaro
    Department of Oral Pathology and Oral Radiology and MediCity Research Laboratory, Faculty of Medicine, University of Turku, Turku, Finland
    J Clin Microbiol 40:886-91. 2002
    ..Thus, the method described here is a very sensitive tool with which to assess the physical state of HPV, which is useful in predicting disease progression...
  53. pmc Structural biology of retroviral DNA integration
    Xiang Li
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Virology 411:194-205. 2011
    ..In this review we discuss the landmarks in the progress of integrase structural biology during the past 17 years...
  54. ncbi Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene
    Patrizia Paterlini-Brechot
    INSERM Pasteur Unit 370, Necker Faculty of Medicine, Necker Enfants Malades Hospital, Paris 75015, France
    Oncogene 22:3911-6. 2003
    ..Thus, HBV frequently targets cellular genes involved in cell signalling and some of them may be preferential targets of the viral integration...
  55. pmc HIV-1 tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter
    G Marzio
    Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology ICGEB, Padriciano 99, 34012 Trieste, Italy
    Proc Natl Acad Sci U S A 95:13519-24. 1998
    ..Additionally, these findings have important implications for the understanding of the mechanisms of HIV-1 latency and reactivation...
  56. pmc Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach
    Dong Ding
    Hangzhou Proprium Biotech, Hangzhou, China
    PLoS Genet 8:e1003065. 2012
    ..This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV-related HCC...
  57. pmc LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration
    Ming Chieh Shun
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 21:1767-78. 2007
    ..Akin to yeast retrotransposons, disrupting the lentiviral targeting mechanism significantly perturbs overall integration...
  58. pmc Human papillomavirus type 16 integration in cervical carcinoma in situ and in invasive cervical cancer
    Hugo Arias-Pulido
    Department of Molecular Genetics and Microbiology, School of Medicine, Health Sciences Center, University of New Mexico, Albuquerque, NM 87111, USA
    J Clin Microbiol 44:1755-62. 2006
    ..HPV-16 E2 expressed from intact episomes may act in trans to regulate integrated genome expression of E6 and E7...
  59. pmc APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms
    Jean L Mbisa
    HIV Drug Resistance Program, National Cancer Institute at Frederick, P O Box B, Building 535, Room 334, Frederick, MD 21702 1201, USA
    J Virol 84:5250-9. 2010
    ....
  60. pmc Viral protein R regulates nuclear import of the HIV-1 pre-integration complex
    S Popov
    The Picower Institute for Medical Research, Manhasset, NY 11030, USA
    EMBO J 17:909-17. 1998
    ..These results identify the biochemical mechanism of Vpr function in transport of the viral pre-integration complex to, and across, the nuclear membrane...
  61. pmc Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts
    Arianna Moiani
    Division of Genetics and Cell Biology, Istituto Scientifico H San Raffaele, Milan, Italy
    J Clin Invest 122:1653-66. 2012
    ..A limited set of cryptic splice sites caused the majority of aberrant splicing events, providing a strategy for recoding lentiviral vector backbones and transgenes to reduce their potential posttranscriptional genotoxicity...
  62. pmc Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus
    Xiang Li
    Address correspondence to Alan Engelman
    J Virol 86:3861-79. 2012
    ....
  63. pmc Gammaretroviral integration into nucleosomal target DNA in vivo
    Shoshannah L Roth
    University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104 6076, USA
    J Virol 85:7393-401. 2011
    ..Thus, we conclude that favored integration near DNase I-hypersensitive sites does not imply that integration takes place exclusively in nucleosome-free regions...
  64. pmc Herpesviruses and chromosomal integration
    Guillaume Morissette
    Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Quebec, Quebec, Canada
    J Virol 84:12100-9. 2010
    ..In this review, we provide a historical perspective on chromosomal integration by herpesviruses and present the current state of knowledge on integration by HHV-6 with the possible clinical implications associated with viral integration...
  65. pmc HIV-1 integrates into resting CD4+ T cells even at low inoculums as demonstrated with an improved assay for HIV-1 integration
    Luis M Agosto
    Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 3905, USA
    Virology 368:60-72. 2007
    ..These findings suggest there is no threshold number of virions required for HIV to integrate into resting CD4(+) T cells...
  66. ncbi Recurrent integration of human papillomaviruses 16, 45, and 67 near translocation breakpoints in new cervical cancer cell lines
    L A Koopman
    Department of Pathology, Leiden University Medical Center, The Netherlands
    Cancer Res 59:5615-24. 1999
    ..The detection of multiple HPV integration sites at rearranged chromosomes at such high frequency in cervical cancer-derived cells may reflect events that are relevant to the development of cervical cancer...
  67. pmc Functional coupling between HIV-1 integrase and the SWI/SNF chromatin remodeling complex for efficient in vitro integration into stable nucleosomes
    Paul Lesbats
    Laboratoire MCMP, UMR 5234 CNRS Université Victor Segalen Bordeaux 2, Bordeaux, France
    PLoS Pathog 7:e1001280. 2011
    ..Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier...
  68. ncbi Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro
    Kersten K Koelsch
    University of California, San Diego, USA
    J Infect Dis 197:411-9. 2008
    ..Recent studies report an association between HIV-1 DNA levels, disease progression, and treatment outcome. However, HIV-1 DNA exists as distinct molecular forms that are not distinguished by conventional assays...
  69. pmc Integration target site selection by a resurrected human endogenous retrovirus
    Troy Brady
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 23:633-42. 2009
    ..These findings indicate that accumulation of HERVs in the human germline is a two-step process: integration targeting biases direct initial accumulation, then purifying selection leads to loss of proviruses disrupting gene function...
  70. pmc Deciphering the code for retroviral integration target site selection
    Federico Andrea Santoni
    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    PLoS Comput Biol 6:e1001008. 2010
    ....
  71. pmc HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP
    Kiran N Meekings
    Department of Immunology, Wright Fleming Institute, Imperial College London, London, United Kingdom
    PLoS Pathog 4:e1000027. 2008
    ....
  72. ncbi HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase
    P Gallay
    Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 83:569-76. 1995
    ..It is blocked by phosphotyrosine, indicating that IN recognizes the phosphorylated C-terminal residue of MA. These results explain how the karyophilic potential of MA is conferred to the HIV nucleoprotein complex...
  73. pmc HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear pore
    Nathalie J Arhel
    Groupe de Virologie Moléculaire et Vectorologie, CNRS URA 3015, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    EMBO J 26:3025-37. 2007
    ..These data show that DNA Flap formation, the very last event of HIV-1 RT degrees, acts as a viral promoting element for the uncoating of HIV-1 at the nuclear pore...
  74. pmc Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas
    Y Murakami
    Department of Gastroenterology, Fukui National Hospital, 33 1 Sakuragaoka, Tsuruga, Fukui 914 0195, Japan
    Gut 54:1162-8. 2005
    ..We have previously shown that viral integration can lead to aberrant target gene transcription. In this study, we attempted to investigate common pathways to hepatocarcinogenesis...
  75. pmc Viral complementation allows HIV-1 replication without integration
    Huub C Gelderblom
    Department of Basic Sciences and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA
    Retrovirology 5:60. 2008
    ..Here we examine the influence of an integrated provirus on unintegrated HIV-1 DNA (uDNA)...
  76. pmc Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell
    Luca Biasco
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milano, Italy
    EMBO Mol Med 3:89-101. 2011
    ..Our study shows that MLV vector insertional profile is cell-specific according to the genetic/chromatin state of the target cell both in vitro and in vivo in patients several years after GT...
  77. ncbi Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis
    Mark A Feitelson
    Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
    Cancer Lett 252:157-70. 2007
    ..If so, then selected integration events may alter pathways that are rate limiting in hepatocarcinogenesis, thereby providing targets with diagnostic/prognostic potential and for therapeutic intervention...
  78. ncbi Yeast two-hybrid detection of integrase-host factor interactions
    Jean Christophe Rain
    Hybrigenics S A, 3 5 Impasse Reille, Paris 75014, France
    Methods 47:291-7. 2009
    ..All tolled, our studies identified LEDGF/p75, Transportin-SR2 (TNPO3), von Hippel-Lindau binding protein 1 (VBP1), and sucrose non-fermenting 5 (SNF5) as cellular binding partners of HIV-1 integrase...
  79. ncbi Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5
    G V Kalpana
    Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, NY 10032
    Science 266:2002-6. 1994
    ..The gene, termed INI1 (for integrase interactor 1), may encode a nuclear factor that promotes integration and targets incoming viral DNA to active genes...
  80. ncbi Hot spots of retroviral integration in human CD34+ hematopoietic cells
    Claudia Cattoglio
    Italian Institute of Technology, Unit of Molecular Neuroscience, Istituto Scientifico H San Raffaele, Milan, Italy
    Blood 110:1770-8. 2007
    ..The lower propensity of LV vectors for integrating in potentially dangerous regions of the human genome may be a factor determining a better safety profile for gene therapy applications...
  81. pmc In vitro HIV-1 selective integration into the target sequence and decoy-effect of the modified sequence
    Tatsuaki Tsuruyama
    Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto Prefecture, Japan
    PLoS ONE 5:e13841. 2010
    ....
  82. ncbi The regulation of HIV-1 gene expression: the emerging role of chromatin
    Guocheng He
    University of Texas Southwestern Medical Center at Dallas, Department of Medicine, Division of Infectious Diseases, Dallas, Texas 75390 9113, USA
    DNA Cell Biol 21:697-705. 2002
    ..A better understanding of the role of chromatin in the regulation of HIV expression could lead to much-needed therapies against proviral genomes that are being actively transcribed, and those that are quiescent and persistent...
  83. ncbi Identification of human papillomavirus type 16 integration sites in high-grade precancerous cervical lesions
    Mihaela Matovina
    Rudjer Boskovic Institute, Department of Molecular Medicine, Zagreb, Croatia
    Gynecol Oncol 113:120-7. 2009
    ....
  84. ncbi Superinfection of defective human immunodeficiency virus type 1 with different subtypes of wild-type virus efficiently produces infectious variants with the initial viral phenotypes by complementation followed by recombination
    Yukie Iwabu
    Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    Microbes Infect 10:504-13. 2008
    ..These findings suggest the significance of long-lived infected cells as recipients for superinfection...
  85. pmc A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences
    William Lowther
    Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, Bethesda, MD 20892, USA
    J Virol 79:10093-6. 2005
    ..Reverse transcriptase PCR results demonstrated that each of the viral insertions led to elevated expression of the presumed target flanking genes...
  86. ncbi Quantitative analysis of lentiviral transgene expression in mice over seven generations
    Yong Wang
    Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China
    Transgenic Res 19:775-84. 2010
    ..Taken together, these data suggested that transgenic lines with long term stable expression and no position effect can be established by lentiviral transgenesis...
  87. pmc Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex
    David J Dismuke
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A 5301 Medical Center North, Nashville, Tennessee 37232 2363, USA
    J Virol 80:3712-20. 2006
    ..These results demonstrate that mutations in CA can have deleterious effects on both nuclear targeting and integration, suggesting that these steps in the HIV-1 life cycle are dependent on proper uncoating of the viral core...
  88. pmc High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region
    Jan De Rijck
    Laboratory for Molecular Virology and Gene Therapy, KULeuven and IRC KULAK, Kapucijnenvoer 33, B 3000 Leuven, Belgium
    Nucleic Acids Res 38:6135-47. 2010
    ..Interestingly, some associations did not correlate with HIV-1 integration indicating that not all LEDGF/p75 complexes on the chromosome are amenable to HIV-1 integration...
  89. ncbi MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors
    M Peter
    Departement de Biologie des Tumeurs, Institut Curie, Paris, Cedex, France
    Oncogene 25:5985-93. 2006
    ..MYC activation, triggered by the insertion of HPV DNA sequences, can be an important genetic event in cervical oncogenesis...
  90. pmc Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition
    M D Miller
    Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Virol 71:5382-90. 1997
    ..Only molecules correctly cleaved by integrase protein at the 3' ends were competent to integrate, suggesting that one role for terminal cleavage by integrase may be to create a defined end at otherwise heterogeneous cDNA termini...
  91. ncbi The TRIM family protein KAP1 inhibits HIV-1 integration
    Awatef Allouch
    Molecular Biology Laboratory, Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa 56126, Italy
    Cell Host Microbe 9:484-95. 2011
    ..This study identifies KAP1 as a cellular factor restricting HIV-1 infection and underscores the relevance of IN acetylation as a crucial step in the viral infectious cycle...
  92. pmc Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton
    Paul U Cameron
    Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria 3004, Australia
    Proc Natl Acad Sci U S A 107:16934-9. 2010
    ..We propose a unique pathway for establishment of latency by direct HIV-1 infection of resting CD4(+) T cells during normal chemokine-directed recirculation of CD4(+) T cells between blood and tissue...
  93. pmc Modification of integration site preferences of an HIV-1-based vector by expression of a novel synthetic protein
    Robert M Silvers
    Division of Infectious Diseases, Center for Human Virology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Hum Gene Ther 21:337-49. 2010
    ..These data provide a novel approach to address the problem of the tendency of retroviral vectors to integrate at undesirable sites of the human genome...
  94. ncbi Silencing and variegation of gammaretrovirus and lentivirus vectors
    James Ellis
    Developmental Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G 1L7
    Hum Gene Ther 16:1241-6. 2005
    ..It will therefore be important to further characterize the mechanisms of silencing, in order to create better gammaretrovirus and lentivirus vectors that consistently express at single copy for gene therapy...
  95. pmc Constraints on the dominant mechanism for HIV viral dynamics in patients on raltegravir
    Ahmad R Sedaghat
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Antivir Ther 14:263-71. 2009
    ..Alternative explanations for this phenomenon are also possible. For example, the stage in the viral life cycle at which raltegravir acts might explain the distinct viral dynamics produced by this drug...
  96. pmc Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6076, USA
    Blood 115:4356-66. 2010
    ..The approaches to sequencing and bioinformatics analysis reported here should be widely useful in assessing the outcome of gene therapy trials...
  97. pmc Complete association between a retroviral insertion in the tyrosinase gene and the recessive white mutation in chickens
    Chung Ming Chang
    UMR Génétique et Diversité Animales, INRA INA P G, Centre de Recherches de Jouy, 78352 Jouy en Josas, France
    BMC Genomics 7:19. 2006
    ..The albino mutation was found to be a 6 bp deletion in the tyrosinase (TYR) gene. The present work describes an approach to identify the structural rearrangement in the TYR gene associated with the recessive white mutation...
  98. pmc HIV integration site distributions in resting and activated CD4+ T cells infected in culture
    Troy Brady
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    AIDS 23:1461-71. 2009
    ..The goal of this study was to investigate whether the location of HIV integration differs in resting versus activated T cells, a feature that could contribute to the formation of latent viral reservoirs via effects on integration targeting...
  99. ncbi Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA
    Keiko Tanaka-Taya
    Department of Developmental Medicine Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan
    J Med Virol 73:465-73. 2004
    ..These cases shared no clinical features, and included three healthy individuals. Our data suggest that CIHHV-6 is rare but detectable in the general population and that hereditary transmission is one of the routes of HHV-6 transmission...
  100. pmc Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology
    S M A Kulmala
    Department of Oral Pathology, Institute of Dentistry, University of Turku, Finland
    J Clin Pathol 59:513-7. 2006
    ....
  101. pmc Unexpected inheritance: multiple integrations of ancient bornavirus and ebolavirus/marburgvirus sequences in vertebrate genomes
    Vladimir A Belyi
    Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, USA
    PLoS Pathog 6:e1001030. 2010
    ..Clearly, the sources of genetic information in vertebrate genomes are much more diverse than previously suspected...

Research Grants62

  1. Herpesvirus-induced telomerase dysregulation and tumor formation
    Keith William Jarosinski; Fiscal Year: 2011
    ..b>Virus integration sites will be determined by cloning and sequencing of cloned cellular DNA, which are positive for MDV ..
  2. Testing the safety and efficacy of inhibitory RNA mediated purine analog resistan
    Christopher C Porter; Fiscal Year: 2010
    ..cells and 2) determine the toxicity of lentivirus delivered iPAR and treatment with 6TG as it relates to virus integration into the genome...
  3. DNA VIRUS AS VECTORS FOR CARDIOVASCULAR DISEASES
    James M Wilson; Fiscal Year: 2013
    ..The grant will do all pre-clinical studies necessary to begin clinical trials. ..
  4. Targeting the ETS Transcription Factor Rearrangement EWS/FLI in Ewing's Sarcoma
    Kimberly Stegmaier; Fiscal Year: 2013
    ..adult cancer that results from a translocation that fuses the DNA binding domain of the Friend leukemia virus integration 1 (FLI1) transcription factor to the transactivation domain of the EWS protein, forming a fusion EWS/FLI ..
  5. BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATION
    ALAN N ENGELMAN; Fiscal Year: 2013
    ..have previously highlighted that integrase works in close association with cellular factors to accomplish virus integration. The key factor, lens epithelium-derived growth factor (LEDGF), tethers HIV-1 to active genes during ..
  6. GLYCOLYTIC & PEROXISOMAL GENES ON CHROMOSOME 11 AND 12
    GAIL BRUNS; Fiscal Year: 1993
    ..together with 3 reference loci (catalase, beta subunit of follicle stimulating hormone and a hepatitis B virus integration site)...
  7. AUTONOMOUS PARVOVIRUS VECTORS FOR GENE TRANSFER IN SKIN
    IAN MAXWELL; Fiscal Year: 2002
    ..mechanism of persistent expression from APVs is not yet understood it has been shown that autonomous parvo virus integration can occur in a model system...
  8. SUPPRESSION OF HIV REPLICATION BY CD8+ CELLS
    Jay Levy; Fiscal Year: 2000
    ..It blocks the expression of viral RNA but does not affect steps prior to virus integration. CAF is stable to heat and low pH, has a size of 30Kd or less and is inactivated by certain proteases...
  9. SUPPRESSION OF HIV REPLICATION BY CD8+ CELLS
    Jay Levy; Fiscal Year: 2001
    ..It blocks the expression of viral RNA but does not affect steps prior to virus integration. CAF is stable to heat and low pH, has a size of 30 kD or less and is inactivated by certain proteases...
  10. MECHANISM OF NON-INTEGRASE-MEDIATED HIV-1 REPLICATION
    Alan Engelman; Fiscal Year: 2001
    ..Further aims are to develop gene therapy vectors based on non-integrating retroviruses. ..
  11. LEDGF-Integrase Structural Biology
    Alan Engelman; Fiscal Year: 2005
    ..abstract_text> ..
  12. BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATION
    Alan Engelman; Fiscal Year: 2009
    ..of how HIV-1 accomplishes its integration in human cells, which will contribute to the pharmacological goal of developing drugs that effectively inhibit virus integration during the development of AIDS in humans.
  13. MECHANISM OF HIV DNA INTEGRATION
    Frederic Bushman; Fiscal Year: 2005
    ..Long term, these studies, together with data on protein structures, will provide a high-resolution picture of the organization and function of preintegration complexes. ..
  14. Chemistry of HIV-1 Integrase Function
    Frederic Bushman; Fiscal Year: 2007
    ..The Specific Aims are: Aim 1. Functional studies of IN-DNA complexes Aim 2. Structural analysis of IN-DNA complexes. ..
  15. Cellular Response to Retroviral DNA Integration
    Rene Daniel; Fiscal Year: 2007
    ..They should also significantly enhance our understanding of the function of these important cellular pathways. [unreadable] [unreadable]..
  16. 2007 Molecular Biology of Hepatitis B Viruses Meeting
    William Mason; Fiscal Year: 2007
    ..Limited support for meeting materials and organizational[unreadable] functions is also needed. ..
  17. Purchase of the Roche GS SLX Sequencing System
    Frederic Bushman; Fiscal Year: 2008
    ..The instrument will be housed in the University of Pennsylvania School of Medicine DNA Sequencing Core Facility, and be operated by their staff. [unreadable] [unreadable] [unreadable]..
  18. HEPADNAVIRUS INFECTIONS AND LIVER CANCER
    William Mason; Fiscal Year: 2009
    ..abstract_text> ..
  19. MOLLUSCUM CONTAGIOSUM VIRUS TOPOISOMERASE
    Frederic Bushman; Fiscal Year: 2002
    ..In addition, poxviruses have been implicated as possible biological warfare agents; thus poxvirus topoisomerase inhibitors might be use for treating such infections. ..
  20. Macrophages Role in the Development of HIV Lipoatrophy
    Deirdre Killebrew; Fiscal Year: 2008
    ..abstract_text> ..
  21. Targeting Brain Macrophages by a novel lentiviral vector
    Yuntao Wu; Fiscal Year: 2006
    ..abstract_text> ..
  22. Transferring integrase technology to animals
    MICHELE CALOS; Fiscal Year: 2006
    ..By scaling up to animals more similar to humans, these experiments will move the site-specific integrase technology closer to the clinic. [unreadable] [unreadable] [unreadable]..
  23. AVIAN RETROVIRUS DNA SYNTHESIS AND INTEGRATION
    Duane Grandgenett; Fiscal Year: 2008
    ....
  24. Retinal Gene Therapy by Site-Specific Integration
    MICHELE CALOS; Fiscal Year: 2006
    ..These experiments will move the phiC31 integrase [unreadable] [unreadable] [unreadable]..
  25. Congenital HHV6 Infection: Characteristics and Outcome
    Caroline Hall; Fiscal Year: 2007
    ..Correlation of these measurements with the viral and clinical characteristics in Aim I may allow early identification of risk factors that are predictive of future disabilities. ..
  26. Determine the Transcriptional Activity of Non-integrated HIV-1 DNA
    Yuntao Wu; Fiscal Year: 2008
    ..Additionally, non-integrated viral DNA could serve as clinical markers for disease progression in certain situation. [unreadable] [unreadable] [unreadable]..
  27. Custom integration tools for functional genomics
    MICHELE CALOS; Fiscal Year: 2003
    ..We develop the appropriate DNA shuffling and genetic screening methods here for generation of a library of custom integration tools. The strategy is scalable to reach essentially all genes in the mouse genome. ..
  28. CONSTRUCTION AND ANALYSIS OF RETROVIRUS MUTANTS
    Stephen Goff; Fiscal Year: 2003
    ..In each case, these tests will be applied to existing panels of mutants to help localize the regions needed for these activities. ..
  29. HIV-1 INTEGRATION
    Duane Grandgenett; Fiscal Year: 2005
    ..We will continue to investigate the role HIV-1 IN has in the retrovirus life cycle with emphasis on understanding full-site integration. ..
  30. SITE-SPECIFIC INTEGRATION FOR GENE THERAPY
    MICHELE CALOS; Fiscal Year: 2003
    ..The novel site-specific integration strategy developed here can be used to add value to most current gene therapy vectors. ..
  31. PRIMARY HHV6 INFECTION--CLINICAL & VIRAL CHARACTERISTICS
    Caroline Hall; Fiscal Year: 2001
    ..A matched subgroup of 180 (90 with seizures from HHV-6 and 90 with seizures not from HHV-6) will be compared for neurologic development after 3 years by neurologic examinations and standardized neuropsychologic testing. ..
  32. ANIMAL MODELS OF AIDS--POLYTAR INHIBITION OF SIV
    David Strayer; Fiscal Year: 2001
    ..Studies proposed here in nonhuman primates will help to define the utility of this approach to AIDS therapy. ..
  33. Oxadaizols: Rationally designed compounds targeting HIV nuclear importation
    Michael Bukrinsky; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  34. A Novel Inhibitor of Stat3 for Prostate Cancer Therapy
    Naijie Jing; Fiscal Year: 2009
    ..abstract_text> ..
  35. Targeting the CaM Kinases in Treating Myeloid Leukemia
    Steven Collins; Fiscal Year: 2009
    ....
  36. Interaction in vivo between HIV and Hepatitis B Virus
    Sharon Lewin; Fiscal Year: 2005
    ..abstract_text> ..
  37. HTS for inhibitors of HIV-1 latency establishement
    Olaf Kutsch; Fiscal Year: 2010
    ..In this application, we propose to perform drug screening for inhibitors of latency formation with the mid- to long-tem goal of developing drugs to be used in HIV-1 therapy with the intention of viral eradication. ..
  38. SV40 T Antigen Role in Virus Growth and Transformation
    James M Pipas; Fiscal Year: 2010
    ..3. Distinguish the relative roles of the T antigen HR domain and the viral miRNAs in SV40 infection. 4. Determine whether T antigen autoregulation contribute to CTL evasion? ..
  39. TMRNA AND TRANS TRANSLATION--MECHANISM AND BIOLOGY
    Kelly Williams; Fiscal Year: 2003
    ..5) Analyze structure of tmRNA alone and in trans-translation complexes by chemical probing, cross-linking, crystallographic, and electron micrographic (the latter two collaborative) approaches. ..
  40. TRANSCRIPTIONAL REGULATION AND TUMORIGENESIS BY MMTV
    JAQUELIN DUDLEY; Fiscal Year: 2002
    ..Finally, mutations of Cux and SATB1 binding sites and MMTV Sag will be introduced into a full-length infectious MMTV provirus in order to evaluate the role of these elements in the induction of T-cell lymphoma. ..
  41. Enhancement of the Baculovirus Expression Vector System
    Bruce Webb; Fiscal Year: 2008
    ..The enhanced BEVS technology to be developed with this award has potential to significantly improve efficacy of protein production in all such medical applications. [unreadable] [unreadable] [unreadable]..
  42. Imaging Technology for HIV Nuclear Import Inhibitors
    Michael Bukrinsky; Fiscal Year: 2003
    ..The imaging technology will greatly augment the value of the project by adding a superior method for analyzing the activity of the drugs. ..
  43. NUCLEAR TRANSLOCATION OF HIV 1 GENOME AS A DRUG TARGET
    Michael Bukrinsky; Fiscal Year: 2004
    ..Upon completion, these studies are expected to define potent anti-HIV compounds working through a novel mechanism different from that of any other currently used drug. ..
  44. CD4+ memory T cell recruitment by cyclophilin
    Michael Bukrinsky; Fiscal Year: 2004
    ..Therefore, the R03 mechanism appears highly appropriate. If proven, this hypothesis will serve as a foundation for a new research program, which might suggest novel approaches to treatment of HIV-1 infection. ..
  45. STEREOCHEMISTRY OF SITE SPECIFIC RECOMBINATION
    GREGORY VAN DUYNE; Fiscal Year: 2006
    ..abstract_text> ..
  46. Purchase of an Automated HT Real-Time PCR System
    Paul Lieberman; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  47. EXPRESSION AND PATHOGENESIS OF MURINE LEUKEMIA VIRUS
    Hung Fan; Fiscal Year: 2005
    ..low expression. Together, these experiments will provide new and important insights into leukemogenesis by MuLVs. ..
  48. Functions of the General Coactivator TFIIA
    Paul Lieberman; Fiscal Year: 2005
    ....
  49. Mechanisms of HIV-1 proviral inactivation vs latency
    UNA O DOHERTY; Fiscal Year: 2006
    ....
  50. A GFP Based HTS Assay for HIV-1 Tat Inhibitors (RMI)
    Olaf Kutsch; Fiscal Year: 2004
    ..In this application, we propose to transfer the reporter assay to a 384-weil plate format and to establish several counter-screen and verification assays that will allow for the rapid and reliable screen of large compound libraries. ..
  51. FOCUSING IMMUNITY vs BOTULINUM TOXIN WITH CYTOKINE DNA
    David Strayer; Fiscal Year: 2007
    ..abstract_text> ..
  52. OVINE INTERFERON-TAU REGULATES UTERINE HORMONE RECEPTOR
    Fuller Bazer; Fiscal Year: 2005
    ....
  53. PROTECTING CNS CELLS FROM HIV AND HIV-INDUCED INJURY
    David Strayer; Fiscal Year: 2004
    ..We propose to address this therapeutic challenge using rSV40 gene delivery to the CNS, both to protect the brain from HIV infection and to mitigate HIV-induced CNS dysfunction. ..
  54. OVERCOMING POSITION EFFECTS WITH CHROMATIN INSULATORS
    David Emery; Fiscal Year: 2008
    ..abstract_text> ..
  55. GLOBIN GENE TRANSFER FOR THERAPY OF SICKLE CELL ANEMIA
    Michel Sadelain; Fiscal Year: 2004
    ....
  56. HIV infection of male genital tissue (R21)
    Robin Shattock; Fiscal Year: 2005
    ..abstract_text> ..