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Alan N. Engelman, PhD

Alan N. Engelman, PhD

Researcher
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(617) 632 4361

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(617) 632 4338

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Biography

Alan N. Engelman, PhD

Dr. Engelman received his PhD in 1990 from Tufts University School of Medicine and his postdoctoral training at the National Institute of Diabetes, Digestive, and Kidney Diseases. He joined DFCI in 1995, where he conducts research on the mechanism of HIV-1 integration and teaches PhD candidates in the graduate program in virology at Harvard Medical School.

Researcher

Physician

Principal Investigator, Cancer Immunology and Virology, Dana-Farber Cancer Institute
Professor of Medicine, Harvard Medical School

Research

    View Dr. Engelman’s Research

    Retroviral DNA integration

    Our studies focus on the mechanism of human immunodeficiency virus type 1 (HIV-1) integration, an essential step in the viral lifecycle. Retroviruses encode their own integrase protein, and our research borrows from numerous disciplines, including molecular virology and structural biology, to understand mechanistic details of integrase function. Integrase active site inhibitors have been in the clinic since 2007, but until recently their mode of action was largely speculative. Novel X-ray crystal structures of the related spumavirus integrase with its DNA substrate yielded unprecedented details of the structural basis of retroviral DNA integration and, moreover, established how the inhibitors work. Lentiviruses like HIV-1 preferentially target active genes during integration. We established that an interaction between integrase and the cellular chromatin binding protein lens epithelium-derived growth factor (LEDGF) plays a significant role in HIV integration targeting.

    We have recently solved the 3-dimensional structure of the LEDGF/p75 integrase-binding domain (IBD) by NMR spectroscopy, as well as the x-ray structure of the IBD bound to the integrase catalytic core domain, the first structure of a host protein bound to a retroviral enzyme. Other studies have elucidated the LEDGF/p75 binding pocket on integrase as a sensitive binding site for allosteric inhibitors, unveiling a new location for targeting of second-generation integrase inhibitors. Current approaches include screening chemical libraries to identify small molecule inhibitors of the protein-protein interaction to evaluate their potential to block HIV-1 replication in cell culture.

    Research Departments

    Research Website

    https://engelmanlab.dana-farber.org/

    Publications

      View Dr. Engelman's Publications

      • Pathways and Intersections: Multifaceted Approaches to Engage Individuals From Underrepresented and Marginalized Communities in HIV Research and Career Development. J Acquir Immune Defic Syndr. 2023 10 01; 94(2S):S116-S121. View in: Pubmed

      • Capsid-host interactions for HIV-1 ingress. Microbiol Mol Biol Rev. 2023 Sep 26; e0004822. View in: Pubmed

      • Viral and Host Mediators of Non-Suppressible HIV-1 Viremia. medRxiv. 2023 Mar 31. View in: Pubmed

      • The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores. Proc Natl Acad Sci U S A. 2023 03 28; 120(13):e2202815120. View in: Pubmed

      • Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels. Nat Struct Mol Biol. 2023 04; 30(4):425-435. View in: Pubmed

      • The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function. mBio. 2023 02 28; 14(1):e0356022. View in: Pubmed

      • Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection. Nat Commun. 2022 10 06; 13(1):5879. View in: Pubmed

      • Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors. Viruses. 2022 08 26; 14(9). View in: Pubmed

      • B-to-A transition in target DNA during retroviral integration. Nucleic Acids Res. 2022 Aug 26; 50(15):8898-8918. View in: Pubmed

      • Localization and functions of native and eGFP-tagged capsid proteins in HIV-1 particles. PLoS Pathog. 2022 08; 18(8):e1010754. View in: Pubmed

      • Genome-wide CRISPR/Cas9 transcriptional activation screen identifies a histone acetyltransferase inhibitor complex as a regulator of HIV-1 integration. Nucleic Acids Res. 2022 07 08; 50(12):6687-6701. View in: Pubmed

      • Multivalent interactions essential for lentiviral integrase function. Nat Commun. 2022 05 03; 13(1):2416. View in: Pubmed

      • Multimodal Functionalities of HIV-1 Integrase. Viruses. 2022 04 28; 14(5). View in: Pubmed

      • Spatial and Genomic Correlates of HIV-1 Integration Site Targeting. Cells. 2022 02 14; 11(4). View in: Pubmed

      • HIV-1 integrase binding to genomic RNA 5'-UTR induces local structural changes in vitro and in virio. Retrovirology. 2021 11 22; 18(1):37. View in: Pubmed

      • Deep-learning in situ classification of HIV-1 virion morphology. Comput Struct Biotechnol J. 2021; 19:5688-5700. View in: Pubmed

      • Intra- and extra-cellular environments contribute to the fate of HIV-1 infection. Cell Rep. 2021 08 31; 36(9):109622. View in: Pubmed

      • A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. PLoS Pathog. 2021 07; 17(7):e1009671. View in: Pubmed

      • rigrag: high-resolution mapping of genic targeting preferences during HIV-1 integration in vitro and in vivo. Nucleic Acids Res. 2021 07 21; 49(13):7330-7346. View in: Pubmed

      • Structure and function of retroviral integrase. Nat Rev Microbiol. 2022 01; 20(1):20-34. View in: Pubmed

      • Cleavage and Polyadenylation Specificity Factor 6 Is Required for Efficient HIV-1 Latency Reversal. mBio. 2021 06 29; 12(3):e0109821. View in: Pubmed

      • You can keep your coat on. Elife. 2021 06 01; 10. View in: Pubmed

      • Long-Acting Cabotegravir for HIV/AIDS Prophylaxis. Biochemistry. 2021 06 08; 60(22):1731-1740. View in: Pubmed

      • Cytoplasmic CPSF6 Regulates HIV-1 Capsid Trafficking and Infection in a Cyclophilin A-Dependent Manner. mBio. 2021 03 23; 12(2). View in: Pubmed

      • Cryo-EM structure of the Rous sarcoma virus octameric cleaved synaptic complex intasome. Commun Biol. 2021 03 12; 4(1):330. View in: Pubmed

      • D614G and SARS-CoV-2 replication fitness. Signal Transduct Target Ther. 2021 03 01; 6(1):99. View in: Pubmed

      • Factors that mold the nuclear landscape of HIV-1 integration. Nucleic Acids Res. 2021 01 25; 49(2):621-635. View in: Pubmed

      • HIV Capsid and Integration Targeting. Viruses. 2021 Jan 18; 13(1). View in: Pubmed

      • Capsid Lattice Destabilization Leads to Premature Loss of the Viral Genome and Integrase Enzyme during HIV-1 Infection. J Virol. 2020 12 22; 95(2). View in: Pubmed

      • Permeability of the HIV-1 capsid to metabolites modulates viral DNA synthesis. PLoS Biol. 2020 12; 18(12):e3001015. View in: Pubmed

      • Publisher Correction: HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains. Nat Commun. 2020 Nov 26; 11(1):6165. View in: Pubmed

      • Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020 10 16; 370(6514):360-364. View in: Pubmed

      • CPSF6-Dependent Targeting of Speckle-Associated Domains Distinguishes Primate from Nonprimate Lentiviral Integration. mBio. 2020 09 29; 11(5). View in: Pubmed

      • Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis. Elife. 2020 09 22; 9. View in: Pubmed

      • Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature. 2020 09; 585(7824):261-267. View in: Pubmed

      • Intrinsic curvature of the HIV-1 CA hexamer underlies capsid topology and interaction with cyclophilin A. Nat Struct Mol Biol. 2020 09; 27(9):855-862. View in: Pubmed

      • HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains. Nat Commun. 2020 07 14; 11(1):3505. View in: Pubmed

      • Close-up: HIV/SIV intasome structures shed new light on integrase inhibitor binding and viral escape mechanisms. FEBS J. 2021 01; 288(2):427-433. View in: Pubmed

      • The HIV-1 capsid-binding host factor CPSF6 is post-transcriptionally regulated by the cellular microRNA miR-125b. J Biol Chem. 2020 04 10; 295(15):5081-5094. View in: Pubmed

      • A Peptide Derived from Lens Epithelium-Derived Growth Factor Stimulates HIV-1 DNA Integration and Facilitates Intasome Structural Studies. J Mol Biol. 2020 03 27; 432(7):2055-2066. View in: Pubmed

      • Structural basis of second-generation HIV integrase inhibitor action and viral resistance. Science. 2020 02 14; 367(6479):806-810. View in: Pubmed

      • Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2 mouse model. PLoS Pathog. 2019 12; 15(12):e1008154. View in: Pubmed

      • Dominant Negative MA-CA Fusion Protein Is Incorporated into HIV-1 Cores and Inhibits Nuclear Entry of Viral Preintegration Complexes. J Virol. 2019 11 01; 93(21). View in: Pubmed

      • Multifaceted HIV integrase functionalities and therapeutic strategies for their inhibition. J Biol Chem. 2019 10 11; 294(41):15137-15157. View in: Pubmed

      • A HTRF based competitive binding assay for screening specific inhibitors of HIV-1 capsid assembly targeting the C-Terminal domain of capsid. Antiviral Res. 2019 09; 169:104544. View in: Pubmed

      • Capsid-CPSF6 interaction: Master regulator of nuclear HIV-1 positioning and integration. J Life Sci (Westlake Village). 2019 Jun; 1(1):39-45. View in: Pubmed

      • HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors. Elife. 2019 05 23; 8. View in: Pubmed

      • Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6. Nucleic Acids Res. 2019 05 21; 47(9):4663-4683. View in: Pubmed

      • Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration. Cell Host Microbe. 2018 09 12; 24(3):392-404.e8. View in: Pubmed

      • Cellular and molecular mechanisms of HIV-1 integration targeting. Cell Mol Life Sci. 2018 Jul; 75(14):2491-2507. View in: Pubmed

      • Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation. Mol Cell. 2018 01 04; 69(1):62-74.e4. View in: Pubmed

      • Multiplex single-cell visualization of nucleic acids and protein during HIV infection. Nat Commun. 2017 12 01; 8(1):1882. View in: Pubmed

      • LEDGF/p75 is dispensable for hematopoiesis but essential for MLL-rearranged leukemogenesis. Blood. 2018 01 04; 131(1):95-107. View in: Pubmed

      • Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing. J Biol Chem. 2017 12 01; 292(48):19814-19825. View in: Pubmed

      • CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction. Sci Adv. 2017 09; 3(9):e1701264. View in: Pubmed

      • Capsid-Dependent Host Factors in HIV-1 Infection. Trends Microbiol. 2017 09; 25(9):741-755. View in: Pubmed

      • Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature. 2017 05 25; 545(7655):432-438. View in: Pubmed

      • Structural basis for spumavirus GAG tethering to chromatin. Proc Natl Acad Sci U S A. 2017 05 23; 114(21):5509-5514. View in: Pubmed

      • Retroviral intasomes arising. Curr Opin Struct Biol. 2017 12; 47:23-29. View in: Pubmed

      • Inhibition of HIV-1 Maturation via Small-Molecule Targeting of the Amino-Terminal Domain in the Viral Capsid Protein. J Virol. 2017 05 01; 91(9). View in: Pubmed

      • Retroviral integrase protein and intasome nucleoprotein complex structures. World J Biol Chem. 2017 Feb 26; 8(1):32-44. View in: Pubmed

      • A supramolecular assembly mediates lentiviral DNA integration. Science. 2017 01 06; 355(6320):93-95. View in: Pubmed

      • Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity. Cell Rep. 2016 12 20; 17(12):3178-3192. View in: Pubmed

      • Correction: Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration. PLoS Pathog. 2016 Oct; 12(10):e1005956. View in: Pubmed

      • A New Class of Allosteric HIV-1 Integrase Inhibitors Identified by Crystallographic Fragment Screening of the Catalytic Core Domain. J Biol Chem. 2016 Nov 04; 291(45):23569-23577. View in: Pubmed

      • Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration. PLoS Pathog. 2016 08; 12(8):e1005860. View in: Pubmed

      • Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+ T Cells In Vitro. J Virol. 2016 09 15; 90(18):8059-73. View in: Pubmed

      • Allosteric HIV-1 integrase inhibitors promote aberrant protein multimerization by directly mediating inter-subunit interactions: Structural and thermodynamic modeling studies. Protein Sci. 2016 11; 25(11):1911-1917. View in: Pubmed

      • Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. J Virol. 2016 08 01; 90(15):6918-6935. View in: Pubmed

      • Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74. J Virol. 2016 06 15; 90(12):5808-5823. View in: Pubmed

      • Retroviral DNA Integration. Chem Rev. 2016 10 26; 116(20):12730-12757. View in: Pubmed

      • Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites. J Vis Exp. 2016 Mar 22; (109). View in: Pubmed

      • The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV-1 Integration into Genes. J Biol Chem. 2016 May 27; 291(22):11809-19. View in: Pubmed

      • The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency. ACS Chem Biol. 2016 05 20; 11(5):1313-21. View in: Pubmed

      • Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function. Nature. 2016 Feb 18; 530(7590):358-61. View in: Pubmed

      • A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin. Proc Natl Acad Sci U S A. 2016 Feb 23; 113(8):E1054-63. View in: Pubmed

      • Sites of retroviral DNA integration: From basic research to clinical applications. Crit Rev Biochem Mol Biol. 2016; 51(1):26-42. View in: Pubmed

      • Foreign DNA capture during CRISPR-Cas adaptive immunity. Nature. 2015 Nov 26; 527(7579):535-8. View in: Pubmed

      • Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice. PLoS One. 2015; 10(9):e0137797. View in: Pubmed

      • Distribution and Redistribution of HIV-1 Nucleocapsid Protein in Immature, Mature, and Integrase-Inhibited Virions: a Role for Integrase in Maturation. J Virol. 2015 Oct; 89(19):9765-80. View in: Pubmed

      • Structural basis for retroviral integration into nucleosomes. Nature. 2015 Jul 16; 523(7560):366-9. View in: Pubmed

      • Key determinants of target DNA recognition by retroviral intasomes. Retrovirology. 2015 Apr 30; 12:39. View in: Pubmed

      • Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity. Nature. 2015 Mar 12; 519(7542):193-8. View in: Pubmed

      • Retroviral Integrase Structure and DNA Recombination Mechanism. Microbiol Spectr. 2014 Dec; 2(6). View in: Pubmed

      • The mechanism of H171T resistance reveals the importance of Nd-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase. Retrovirology. 2014 Nov 25; 11:100. View in: Pubmed

      • Host and viral determinants for MxB restriction of HIV-1 infection. Retrovirology. 2014 Oct 25; 11:90. View in: Pubmed

      • Structural insight into HIV-1 restriction by MxB. Cell Host Microbe. 2014 Nov 12; 16(5):627-638. View in: Pubmed

      • Molecular mechanisms of retroviral integration site selection. Nucleic Acids Res. 2014; 42(16):10209-25. View in: Pubmed

      • Engineered hyperactive integrase for concerted HIV-1 DNA integration. PLoS One. 2014; 9(8):e105078. View in: Pubmed

      • Integrase residues that determine nucleotide preferences at sites of HIV-1 integration: implications for the mechanism of target DNA binding. Nucleic Acids Res. 2014 Apr; 42(8):5164-76. View in: Pubmed

      • Structural basis for nuclear import of splicing factors by human Transportin 3. Proc Natl Acad Sci U S A. 2014 Feb 18; 111(7):2728-33. View in: Pubmed

      • Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses. Mol Ther Methods Clin Dev. 2014 Jan 08; 1. View in: Pubmed

      • Retroviral Integrase Structure and DNA Recombination Mechanism. Microbiol Spectr. 2014; 2(6):1-22. View in: Pubmed

      • Multimodal mechanism of action of allosteric HIV-1 integrase inhibitors. Expert Rev Mol Med. 2013 Nov 26; 15:e14. View in: Pubmed

      • Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity. PLoS Pathog. 2013; 9(10):e1003693. View in: Pubmed

      • Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes. Viruses. 2013 Oct 07; 5(10):2483-511. View in: Pubmed

      • Biochemical characterization of novel retroviral integrase proteins. PLoS One. 2013; 8(10):e76638. View in: Pubmed

      • Allosteric inhibition of HIV-1 integrase activity. Curr Opin Chem Biol. 2013 Jun; 17(3):339-45. View in: Pubmed

      • The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2013 May 31; 288(22):15813-20. View in: Pubmed

      • Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. Proc Natl Acad Sci U S A. 2013 May 21; 110(21):8690-5. View in: Pubmed

      • Polymorphic LEDGF/p75 variants support efficient HIV-1 infection ex vivo. AIDS. 2013 Feb 20; 27(4):665-7. View in: Pubmed

      • The host proteins transportin SR2/TNPO3 and cyclophilin A exert opposing effects on HIV-1 uncoating. J Virol. 2013 Jan; 87(1):422-32. View in: Pubmed

      • Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. J Virol. 2013 Jan; 87(1):648-58. View in: Pubmed

      • HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor. Nucleic Acids Res. 2012 Dec; 40(22):11518-30. View in: Pubmed

      • Retroviral integrase proteins and HIV-1 DNA integration. J Biol Chem. 2012 Nov 30; 287(49):40858-66. View in: Pubmed

      • Viral latency and potential eradication of HIV-1. Expert Rev Anti Infect Ther. 2012 Aug; 10(8):855-7. View in: Pubmed

      • Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2012 May 11; 287(20):16801-11. View in: Pubmed

      • The structural biology of HIV-1: mechanistic and therapeutic insights. Nat Rev Microbiol. 2012 03 16; 10(4):279-90. View in: Pubmed

      • Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. J Virol. 2012 Apr; 86(8):4708-14. View in: Pubmed

      • Correlation of recombinant integrase activity and functional preintegration complex formation during acute infection by replication-defective integrase mutant human immunodeficiency virus. J Virol. 2012 Apr; 86(7):3861-79. View in: Pubmed

      • The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J Virol. 2011 Aug; 85(15):7818-27. View in: Pubmed

      • HIV DNA is heavily uracilated, which protects it from autointegration. Proc Natl Acad Sci U S A. 2011 May 31; 108(22):9244-9. View in: Pubmed

      • Impairment of human immunodeficiency virus type-1 integrase SUMOylation correlates with an early replication defect. J Biol Chem. 2011 Jun 10; 286(23):21013-22. View in: Pubmed

      • Differential sensitivities of retroviruses to integrase strand transfer inhibitors. J Virol. 2011 Apr; 85(7):3677-82. View in: Pubmed

      • Structural biology of retroviral DNA integration. Virology. 2011 Mar 15; 411(2):194-205. View in: Pubmed

      • Identification and characterization of persistent intracellular human immunodeficiency virus type 1 integrase strand transfer inhibitor activity. Antimicrob Agents Chemother. 2011 Jan; 55(1):42-9. View in: Pubmed

      • Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc Natl Acad Sci U S A. 2010 Sep 07; 107(36):15910-5. View in: Pubmed

      • Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe. 2010 Mar 18; 7(3):221-33. View in: Pubmed

      • Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration. Proc Natl Acad Sci U S A. 2010 Feb 16; 107(7):3135-40. View in: Pubmed

      • Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010 Mar 11; 464(7286):232-6. View in: Pubmed

      • Transcriptional co-activator LEDGF interacts with Cdc7-activator of S-phase kinase (ASK) and stimulates its enzymatic activity. J Biol Chem. 2010 Jan 01; 285(1):541-54. View in: Pubmed

      • The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integrase. J Virol. 2010 Jan; 84(1):397-406. View in: Pubmed

      • Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Retrovirology. 2009 Oct 19; 6:94. View in: Pubmed

      • Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 2009 Jul; 5(7):e1000515. View in: Pubmed

      • Mechanistic and pharmacological analyses of HIV-1 integration. Methods. 2009 Apr; 47(4):225-8. View in: Pubmed

      • In vivo biotinylation and capture of HIV-1 matrix and integrase proteins. J Virol Methods. 2009 Aug; 159(2):178-84. View in: Pubmed

      • The SET complex acts as a barrier to autointegration of HIV-1. PLoS Pathog. 2009 Mar; 5(3):e1000327. View in: Pubmed

      • Quantitative analysis of HIV-1 preintegration complexes. Methods. 2009 Apr; 47(4):283-90. View in: Pubmed

      • A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS Pathog. 2009 Jan; 5(1):e1000259. View in: Pubmed

      • Isolation and analysis of HIV-1 preintegration complexes. Methods Mol Biol. 2009; 485:135-49. View in: Pubmed

      • Dynamic modulation of HIV-1 integrase structure and function by cellular lens epithelium-derived growth factor (LEDGF) protein. J Biol Chem. 2008 Nov 14; 283(46):31802-12. View in: Pubmed

      • Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. J Virol. 2008 Dec; 82(23):11555-67. View in: Pubmed

      • The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog. 2008 Mar 28; 4(3):e1000046. View in: Pubmed

      • Identification of host proteins required for HIV infection through a functional genomic screen. Science. 2008 Feb 15; 319(5865):921-6. View in: Pubmed

      • Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro. Nucleic Acids Res. 2008 Mar; 36(4):1237-46. View in: Pubmed

      • Subunit-specific protein footprinting reveals significant structural rearrangements and a role for N-terminal Lys-14 of HIV-1 Integrase during viral DNA binding. J Biol Chem. 2008 Feb 29; 283(9):5632-41. View in: Pubmed

      • LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 2007 Jul 15; 21(14):1767-78. View in: Pubmed

      • AIDS/HIV. A reversal of fortune in HIV-1 integration. Science. 2007 Jun 29; 316(5833):1855-7. View in: Pubmed

      • Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol. 2007 Jul; 81(13):7099-110. View in: Pubmed

      • Molecular mechanisms of HIV integration and therapeutic intervention. Expert Rev Mol Med. 2007 Feb 26; 9(6):1-19. View in: Pubmed

      • Characterization of a replication-competent, integrase-defective human immunodeficiency virus (HIV)/simian virus 40 chimera as a powerful tool for the discovery and validation of HIV integrase inhibitors. J Virol. 2007 Apr; 81(8):4381-5. View in: Pubmed

      • LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration. Virology. 2007 Mar 30; 360(1):1-5. View in: Pubmed

      • Wild-type levels of human immunodeficiency virus type 1 infectivity in the absence of cellular emerin protein. J Virol. 2007 Jan; 81(1):166-72. View in: Pubmed

      • Proteasome inhibition reveals that a functional preintegration complex intermediate can be generated during restriction by diverse TRIM5 proteins. J Virol. 2006 Oct; 80(19):9754-60. View in: Pubmed

      • Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. Virology. 2007 Jan 05; 357(1):79-90. View in: Pubmed

      • Transcriptional co-activator p75 binds and tethers the Myc-interacting protein JPO2 to chromatin. J Cell Sci. 2006 Jun 15; 119(Pt 12):2563-71. View in: Pubmed

      • Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1. Virology. 2006 Aug 01; 351(2):404-19. View in: Pubmed

      • Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection. Proc Natl Acad Sci U S A. 2006 May 09; 103(19):7454-9. View in: Pubmed

      • A tripartite DNA-binding element, comprised of the nuclear localization signal and two AT-hook motifs, mediates the association of LEDGF/p75 with chromatin in vivo. Nucleic Acids Res. 2006; 34(5):1653-65. View in: Pubmed

      • Biochemical and genetic analyses of integrase-interacting proteins lens epithelium-derived growth factor (LEDGF)/p75 and hepatoma-derived growth factor related protein 2 (HRP2) in preintegration complex function and HIV-1 replication. Virology. 2006 Mar 15; 346(2):415-26. View in: Pubmed

      • Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proc Natl Acad Sci U S A. 2005 Nov 29; 102(48):17308-13. View in: Pubmed

      • Lys-34, dispensable for integrase catalysis, is required for preintegration complex function and human immunodeficiency virus type 1 replication. J Virol. 2005 Oct; 79(19):12584-91. View in: Pubmed

      • Genetic analyses of conserved residues in the carboxyl-terminal domain of human immunodeficiency virus type 1 integrase. J Virol. 2005 Aug; 79(16):10356-68. View in: Pubmed

      • Solution structure of the HIV-1 integrase-binding domain in LEDGF/p75. Nat Struct Mol Biol. 2005 Jun; 12(6):526-32. View in: Pubmed

      • Genetic analyses of DNA-binding mutants in the catalytic core domain of human immunodeficiency virus type 1 integrase. J Virol. 2005 Feb; 79(4):2493-505. View in: Pubmed

      • The ups and downs of gene expression and retroviral DNA integration. Proc Natl Acad Sci U S A. 2005 Feb 01; 102(5):1275-6. View in: Pubmed

      • HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases. Virology. 2005 Jan 05; 331(1):181-9. View in: Pubmed

      • Class II integrase mutants with changes in putative nuclear localization signals are primarily blocked at a postnuclear entry step of human immunodeficiency virus type 1 replication. J Virol. 2004 Dec; 78(23):12735-46. View in: Pubmed

      • Identification of an evolutionarily conserved domain in human lens epithelium-derived growth factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase. J Biol Chem. 2004 Nov 19; 279(47):48883-92. View in: Pubmed

      • Human cell proteins and human immunodeficiency virus DNA integration. Front Biosci. 2004 Sep 01; 9:3187-208. View in: Pubmed

      • Identification and characterization of a functional nuclear localization signal in the HIV-1 integrase interactor LEDGF/p75. J Biol Chem. 2004 Aug 06; 279(32):33421-9. View in: Pubmed

      • General guidelines for experimenting with HIV. Curr Protoc Immunol. 2004 May; Chapter 12:Unit 12.1. View in: Pubmed

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